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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants</title><author><name sortKey="Fritsche, Lars G" sort="Fritsche, Lars G" uniqKey="Fritsche L" first="Lars G." last="Fritsche">Lars G. Fritsche</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Igl, Wilmar" sort="Igl, Wilmar" uniqKey="Igl W" first="Wilmar" last="Igl">Wilmar Igl</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Cooke Bailey, Jessica N" sort="Cooke Bailey, Jessica N" uniqKey="Cooke Bailey J" first="Jessica N." last="Cooke Bailey">Jessica N. Cooke Bailey</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Grassmann, Felix" sort="Grassmann, Felix" uniqKey="Grassmann F" first="Felix" last="Grassmann">Felix Grassmann</name><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Sengupta, Sebanti" sort="Sengupta, Sebanti" uniqKey="Sengupta S" first="Sebanti" last="Sengupta">Sebanti Sengupta</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Bragg Gresham, Jennifer L" sort="Bragg Gresham, Jennifer L" uniqKey="Bragg Gresham J" first="Jennifer L." last="Bragg-Gresham">Jennifer L. Bragg-Gresham</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Kidney Epidemiology and Cost Center, Department of Internal Medicine - Nephrology, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation></author><author><name sortKey="Burdon, Kathryn P" sort="Burdon, Kathryn P" uniqKey="Burdon K" first="Kathryn P." last="Burdon">Kathryn P. Burdon</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Hebbring, Scott J" sort="Hebbring, Scott J" uniqKey="Hebbring S" first="Scott J." last="Hebbring">Scott J. Hebbring</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Wen, Cindy" sort="Wen, Cindy" uniqKey="Wen C" first="Cindy" last="Wen">Cindy Wen</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Gorski, Mathias" sort="Gorski, Mathias" uniqKey="Gorski M" first="Mathias" last="Gorski">Mathias Gorski</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Kim, Ivana K" sort="Kim, Ivana K" uniqKey="Kim I" first="Ivana K." last="Kim">Ivana K. Kim</name><affiliation><nlm:aff id="A9">Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Cho, David" sort="Cho, David" uniqKey="Cho D" first="David" last="Cho">David Cho</name><affiliation><nlm:aff id="A10">Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Zack, Donald" sort="Zack, Donald" uniqKey="Zack D" first="Donald" last="Zack">Donald Zack</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Molecular Biology and Genetics - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Neuroscience - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institute of Genetic Medicine - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Institue de la Vision, Université Pierre et Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Souied, Eric" sort="Souied, Eric" uniqKey="Souied E" first="Eric" last="Souied">Eric Souied</name><affiliation><nlm:aff id="A16">Hôpital Intercommunal de Créteil, Hôpital Henri Mondor - Université Paris Est Créteil, France</nlm:aff></affiliation></author><author><name sortKey="Scholl, Hendrik P N" sort="Scholl, Hendrik P N" uniqKey="Scholl H" first="Hendrik P. N." last="Scholl">Hendrik P. N. Scholl</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A17">University of Bonn - Department of Ophthalmology, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Bala, Elisa" sort="Bala, Elisa" uniqKey="Bala E" first="Elisa" last="Bala">Elisa Bala</name><affiliation><nlm:aff id="A18">Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Kristine E" sort="Lee, Kristine E" uniqKey="Lee K" first="Kristine E." last="Lee">Kristine E. Lee</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Sardell, Rebecca J" sort="Sardell, Rebecca J" uniqKey="Sardell R" first="Rebecca J." last="Sardell">Rebecca J. Sardell</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Merriam, Joanna E" sort="Merriam, Joanna E" uniqKey="Merriam J" first="Joanna E." last="Merriam">Joanna E. Merriam</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Cipriani, Valentina" sort="Cipriani, Valentina" uniqKey="Cipriani V" first="Valentina" last="Cipriani">Valentina Cipriani</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hoffman, Joshua D" sort="Hoffman, Joshua D" uniqKey="Hoffman J" first="Joshua D." last="Hoffman">Joshua D. Hoffman</name><affiliation><nlm:aff id="A27">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Schick, Tina" sort="Schick, Tina" uniqKey="Schick T" first="Tina" last="Schick">Tina Schick</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Lechanteur, Yara T E" sort="Lechanteur, Yara T E" uniqKey="Lechanteur Y" first="Yara T. E." last="Lechanteur">Yara T. E. Lechanteur</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Guymer, Robyn H" sort="Guymer, Robyn H" uniqKey="Guymer R" first="Robyn H." last="Guymer">Robyn H. Guymer</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Johnson, Matthew P" sort="Johnson, Matthew P" uniqKey="Johnson M" first="Matthew P." last="Johnson">Matthew P. Johnson</name><affiliation><nlm:aff id="A31">South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Jiang, Yingda" sort="Jiang, Yingda" uniqKey="Jiang Y" first="Yingda" last="Jiang">Yingda Jiang</name><affiliation><nlm:aff id="A32">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Stanton, Chloe M" sort="Stanton, Chloe M" uniqKey="Stanton C" first="Chloe M." last="Stanton">Chloe M. Stanton</name><affiliation><nlm:aff id="A33">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Buitendijk, Gabrielle H S" sort="Buitendijk, Gabrielle H S" uniqKey="Buitendijk G" first="Gabriëlle H. S." last="Buitendijk">Gabriëlle H. S. Buitendijk</name><affiliation><nlm:aff id="A34">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhan, Xiaowei" sort="Zhan, Xiaowei" uniqKey="Zhan X" first="Xiaowei" last="Zhan">Xiaowei Zhan</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Quantitative Biomedical Research Center, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Kwong, Alan M" sort="Kwong, Alan M" uniqKey="Kwong A" first="Alan M." last="Kwong">Alan M. Kwong</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Boleda, Alexis" sort="Boleda, Alexis" uniqKey="Boleda A" first="Alexis" last="Boleda">Alexis Boleda</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Brooks, Matthew" sort="Brooks, Matthew" uniqKey="Brooks M" first="Matthew" last="Brooks">Matthew Brooks</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Gieser, Linn" sort="Gieser, Linn" uniqKey="Gieser L" first="Linn" last="Gieser">Linn Gieser</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Ratnapriya, Rinki" sort="Ratnapriya, Rinki" uniqKey="Ratnapriya R" first="Rinki" last="Ratnapriya">Rinki Ratnapriya</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Branham, Kari E" sort="Branham, Kari E" uniqKey="Branham K" first="Kari E." last="Branham">Kari E. Branham</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Foerster, Johanna R" sort="Foerster, Johanna R" uniqKey="Foerster J" first="Johanna R." last="Foerster">Johanna R. Foerster</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Heckenlively, John R" sort="Heckenlively, John R" uniqKey="Heckenlively J" first="John R." last="Heckenlively">John R. Heckenlively</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Othman, Mohammad I" sort="Othman, Mohammad I" uniqKey="Othman M" first="Mohammad I." last="Othman">Mohammad I. Othman</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Vote, Brendan J" sort="Vote, Brendan J" uniqKey="Vote B" first="Brendan J." last="Vote">Brendan J. Vote</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Liang, Helena Hai" sort="Liang, Helena Hai" uniqKey="Liang H" first="Helena Hai" last="Liang">Helena Hai Liang</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Souzeau, Emmanuelle" sort="Souzeau, Emmanuelle" uniqKey="Souzeau E" first="Emmanuelle" last="Souzeau">Emmanuelle Souzeau</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcallister, Ian L" sort="Mcallister, Ian L" uniqKey="Mcallister I" first="Ian L." last="Mcallister">Ian L. Mcallister</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Timothy" sort="Isaacs, Timothy" uniqKey="Isaacs T" first="Timothy" last="Isaacs">Timothy Isaacs</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Hall, Janette" sort="Hall, Janette" uniqKey="Hall J" first="Janette" last="Hall">Janette Hall</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Lake, Stewart" sort="Lake, Stewart" uniqKey="Lake S" first="Stewart" last="Lake">Stewart Lake</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A." last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Constable, Ian J" sort="Constable, Ian J" uniqKey="Constable I" first="Ian J." last="Constable">Ian J. Constable</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Craig, Jamie E" sort="Craig, Jamie E" uniqKey="Craig J" first="Jamie E." last="Craig">Jamie E. Craig</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Kitchner, Terrie E" sort="Kitchner, Terrie E" uniqKey="Kitchner T" first="Terrie E." last="Kitchner">Terrie E. Kitchner</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Yang, Zhenglin" sort="Yang, Zhenglin" uniqKey="Yang Z" first="Zhenglin" last="Yang">Zhenglin Yang</name><affiliation><nlm:aff id="A42">Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China</nlm:aff></affiliation></author><author><name sortKey="Su, Zhiguang" sort="Su, Zhiguang" uniqKey="Su Z" first="Zhiguang" last="Su">Zhiguang Su</name><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Luo, Hongrong" sort="Luo, Hongrong" uniqKey="Luo H" first="Hongrong" last="Luo">Hongrong Luo</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Daniel" sort="Chen, Daniel" uniqKey="Chen D" first="Daniel" last="Chen">Daniel Chen</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ouyang, Hong" sort="Ouyang, Hong" uniqKey="Ouyang H" first="Hong" last="Ouyang">Hong Ouyang</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Flagg, Ken" sort="Flagg, Ken" uniqKey="Flagg K" first="Ken" last="Flagg">Ken Flagg</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Lin, Danni" sort="Lin, Danni" uniqKey="Lin D" first="Danni" last="Lin">Danni Lin</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Mao, Guanping" sort="Mao, Guanping" uniqKey="Mao G" first="Guanping" last="Mao">Guanping Mao</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ferreyra, Henry" sort="Ferreyra, Henry" uniqKey="Ferreyra H" first="Henry" last="Ferreyra">Henry Ferreyra</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Stark, Klaus" sort="Stark, Klaus" uniqKey="Stark K" first="Klaus" last="Stark">Klaus Stark</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Von Strachwitz, Claudia N" sort="Von Strachwitz, Claudia N" uniqKey="Von Strachwitz C" first="Claudia N." last="Von Strachwitz">Claudia N. Von Strachwitz</name><affiliation><nlm:aff id="A45">EyeCentre Southwest, Stuttgart, Baden-Württemberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolf, Armin" sort="Wolf, Armin" uniqKey="Wolf A" first="Armin" last="Wolf">Armin Wolf</name><affiliation><nlm:aff id="A46">University Eye Clinic, Ludwig-Maximilians-University, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Brandl, Caroline" sort="Brandl, Caroline" uniqKey="Brandl C" first="Caroline" last="Brandl">Caroline Brandl</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Guenther" sort="Rudolph, Guenther" uniqKey="Rudolph G" first="Guenther" last="Rudolph">Guenther Rudolph</name><affiliation><nlm:aff id="A46">University Eye Clinic, Ludwig-Maximilians-University, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Olden, Matthias" sort="Olden, Matthias" uniqKey="Olden M" first="Matthias" last="Olden">Matthias Olden</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Morrison, Margaux A" sort="Morrison, Margaux A" uniqKey="Morrison M" first="Margaux A." last="Morrison">Margaux A. Morrison</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Morgan, Denise J" sort="Morgan, Denise J" uniqKey="Morgan D" first="Denise J." last="Morgan">Denise J. Morgan</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Schu, Matthew" sort="Schu, Matthew" uniqKey="Schu M" first="Matthew" last="Schu">Matthew Schu</name><affiliation><nlm:aff id="A49">Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Ahn, Jeeyun" sort="Ahn, Jeeyun" uniqKey="Ahn J" first="Jeeyun" last="Ahn">Jeeyun Ahn</name><affiliation><nlm:aff id="A54">Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Silvestri, Giuliana" sort="Silvestri, Giuliana" uniqKey="Silvestri G" first="Giuliana" last="Silvestri">Giuliana Silvestri</name><affiliation><nlm:aff id="A55">Centre for Experimental Medicine, Queen's University, Belfast, UK</nlm:aff></affiliation></author><author><name sortKey="Tsironi, Evangelia E" sort="Tsironi, Evangelia E" uniqKey="Tsironi E" first="Evangelia E." last="Tsironi">Evangelia E. Tsironi</name><affiliation><nlm:aff id="A56">Department of Ophthalmology, University of Thessaly, School of Medicine, Larissa, Greece</nlm:aff></affiliation></author><author><name sortKey="Park, Kyu Hyung" sort="Park, Kyu Hyung" uniqKey="Park K" first="Kyu Hyung" last="Park">Kyu Hyung Park</name><affiliation><nlm:aff id="A57">Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Farrer, Lindsay A" sort="Farrer, Lindsay A" uniqKey="Farrer L" first="Lindsay A." last="Farrer">Lindsay A. Farrer</name><affiliation><nlm:aff id="A49">Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Orlin, Anton" sort="Orlin, Anton" uniqKey="Orlin A" first="Anton" last="Orlin">Anton Orlin</name><affiliation><nlm:aff id="A58">Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Brucker, Alexander" sort="Brucker, Alexander" uniqKey="Brucker A" first="Alexander" last="Brucker">Alexander Brucker</name><affiliation><nlm:aff id="A59">Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Mingyao" sort="Li, Mingyao" uniqKey="Li M" first="Mingyao" last="Li">Mingyao Li</name><affiliation><nlm:aff id="A60">Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Curcio, Christine" sort="Curcio, Christine" uniqKey="Curcio C" first="Christine" last="Curcio">Christine Curcio</name><affiliation><nlm:aff id="A61">Department of Ophthalmology, The University of Alabama at Birmingham, Birmingham, AL, USA</nlm:aff></affiliation></author><author><name sortKey="Mohand Said, Saddek" sort="Mohand Said, Saddek" uniqKey="Mohand Said S" first="Saddek" last="Mohand-Saïd">Saddek Mohand-Saïd</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Sahel, Jose Alain" sort="Sahel, Jose Alain" uniqKey="Sahel J" first="José-Alain" last="Sahel">José-Alain Sahel</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Fondation Ophtalmologique Adolphe de Rothschild, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Académie des Sciences–Institut de France, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Audo, Isabelle" sort="Audo, Isabelle" uniqKey="Audo I" first="Isabelle" last="Audo">Isabelle Audo</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Department of Molecular Genetics, Institute of Ophthalmology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Benchaboune, Mustapha" sort="Benchaboune, Mustapha" uniqKey="Benchaboune M" first="Mustapha" last="Benchaboune">Mustapha Benchaboune</name><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Cree, Angela J" sort="Cree, Angela J" uniqKey="Cree A" first="Angela J." last="Cree">Angela J. Cree</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Rennie, Christina A" sort="Rennie, Christina A" uniqKey="Rennie C" first="Christina A." last="Rennie">Christina A. Rennie</name><affiliation><nlm:aff id="A70">University Hospital Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Goverdhan, Srinivas V" sort="Goverdhan, Srinivas V" uniqKey="Goverdhan S" first="Srinivas V." last="Goverdhan">Srinivas V. Goverdhan</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Grunin, Michelle" sort="Grunin, Michelle" uniqKey="Grunin M" first="Michelle" last="Grunin">Michelle Grunin</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Hagbi Levi, Shira" sort="Hagbi Levi, Shira" uniqKey="Hagbi Levi S" first="Shira" last="Hagbi-Levi">Shira Hagbi-Levi</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Campochiaro, Peter" sort="Campochiaro, Peter" uniqKey="Campochiaro P" first="Peter" last="Campochiaro">Peter Campochiaro</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Neuroscience - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Katsanis, Nicholas" sort="Katsanis, Nicholas" uniqKey="Katsanis N" first="Nicholas" last="Katsanis">Nicholas Katsanis</name><affiliation><nlm:aff id="A72">Center for Human Disease Modeling, Duke University, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Department of Cell Biology, Duke University, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A74">Department of Pediatrics, Duke University, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Holz, Frank G" sort="Holz, Frank G" uniqKey="Holz F" first="Frank G." last="Holz">Frank G. Holz</name><affiliation><nlm:aff id="A17">University of Bonn - Department of Ophthalmology, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Blond, Frederic" sort="Blond, Frederic" uniqKey="Blond F" first="Frédéric" last="Blond">Frédéric Blond</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Blanche, Helene" sort="Blanche, Helene" uniqKey="Blanche H" first="Hélène" last="Blanché">Hélène Blanché</name><affiliation><nlm:aff id="A75">CEPH Fondation Jean Dausset Paris, France</nlm:aff></affiliation></author><author><name sortKey="Deleuze, Jean Francois" sort="Deleuze, Jean Francois" uniqKey="Deleuze J" first="Jean-François" last="Deleuze">Jean-François Deleuze</name><affiliation><nlm:aff id="A75">CEPH Fondation Jean Dausset Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A76">CEA – IG – Centre National de Génotypage Evry Cédex, France</nlm:aff></affiliation></author><author><name sortKey="Igo, Robert P" sort="Igo, Robert P" uniqKey="Igo R" first="Robert P." last="Igo">Robert P. Igo</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Truitt, Barbara" sort="Truitt, Barbara" uniqKey="Truitt B" first="Barbara" last="Truitt">Barbara Truitt</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Peachey, Neal S" sort="Peachey, Neal S" uniqKey="Peachey N" first="Neal S." last="Peachey">Neal S. Peachey</name><affiliation><nlm:aff id="A18">Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A77">Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Meuer, Stacy M" sort="Meuer, Stacy M" uniqKey="Meuer S" first="Stacy M." last="Meuer">Stacy M. Meuer</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Myers, Chelsea E" sort="Myers, Chelsea E" uniqKey="Myers C" first="Chelsea E." last="Myers">Chelsea E. Myers</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Moore, Emily L" sort="Moore, Emily L" uniqKey="Moore E" first="Emily L." last="Moore">Emily L. Moore</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Ronald" sort="Klein, Ronald" uniqKey="Klein R" first="Ronald" last="Klein">Ronald Klein</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><affiliation><nlm:aff id="A78">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A79">Department of Medicine, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Postel, Eric A" sort="Postel, Eric A" uniqKey="Postel E" first="Eric A." last="Postel">Eric A. Postel</name><affiliation><nlm:aff id="A78">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Courtenay, Monique D" sort="Courtenay, Monique D" uniqKey="Courtenay M" first="Monique D." last="Courtenay">Monique D. Courtenay</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Schwartz, Stephen G" sort="Schwartz, Stephen G" uniqKey="Schwartz S" first="Stephen G." last="Schwartz">Stephen G. Schwartz</name><affiliation><nlm:aff id="A81">Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Kovach, Jaclyn L" sort="Kovach, Jaclyn L" uniqKey="Kovach J" first="Jaclyn L." last="Kovach">Jaclyn L. Kovach</name><affiliation><nlm:aff id="A81">Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Liew, Gerald" sort="Liew, Gerald" uniqKey="Liew G" first="Gerald" last="Liew">Gerald Liew</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="T An, Ava G" sort="T An, Ava G" uniqKey="T An A" first="Ava G." last="T An">Ava G. T An</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Gopinath, Bamini" sort="Gopinath, Bamini" uniqKey="Gopinath B" first="Bamini" last="Gopinath">Bamini Gopinath</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Merriam, John C" sort="Merriam, John C" uniqKey="Merriam J" first="John C." last="Merriam">John C. Merriam</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Smith, R Theodore" sort="Smith, R Theodore" uniqKey="Smith R" first="R. Theodore" last="Smith">R. Theodore Smith</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Ophthalmology, NYU School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Khan, Jane C" sort="Khan, Jane C" uniqKey="Khan J" first="Jane C." last="Khan">Jane C. Khan</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A83">Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Shahid, Humma" sort="Shahid, Humma" uniqKey="Shahid H" first="Humma" last="Shahid">Humma Shahid</name><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A85">Department of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Moore, Anthony T" sort="Moore, Anthony T" uniqKey="Moore A" first="Anthony T." last="Moore">Anthony T. Moore</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Department of Ophthalmology UCSF Medical School, San Francisco, CA USA</nlm:aff></affiliation></author><author><name sortKey="Mcgrath, J Allie" sort="Mcgrath, J Allie" uniqKey="Mcgrath J" first="J. Allie" last="Mcgrath">J. Allie Mcgrath</name><affiliation><nlm:aff id="A27">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Laux, Renee" sort="Laux, Renee" uniqKey="Laux R" first="Reneé" last="Laux">Reneé Laux</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Brantley, Milam A" sort="Brantley, Milam A" uniqKey="Brantley M" first="Milam A." last="Brantley">Milam A. Brantley</name><affiliation><nlm:aff id="A87">Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Agarwal, Anita" sort="Agarwal, Anita" uniqKey="Agarwal A" first="Anita" last="Agarwal">Anita Agarwal</name><affiliation><nlm:aff id="A87">Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Ersoy, Lebriz" sort="Ersoy, Lebriz" uniqKey="Ersoy L" first="Lebriz" last="Ersoy">Lebriz Ersoy</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Caramoy, Albert" sort="Caramoy, Albert" uniqKey="Caramoy A" first="Albert" last="Caramoy">Albert Caramoy</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Langmann, Thomas" sort="Langmann, Thomas" uniqKey="Langmann T" first="Thomas" last="Langmann">Thomas Langmann</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Saksens, Nicole T M" sort="Saksens, Nicole T M" uniqKey="Saksens N" first="Nicole T. M." last="Saksens">Nicole T. M. Saksens</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Jong, Eiko K" sort="De Jong, Eiko K" uniqKey="De Jong E" first="Eiko K." last="De Jong">Eiko K. De Jong</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hoyng, Carel B" sort="Hoyng, Carel B" uniqKey="Hoyng C" first="Carel B." last="Hoyng">Carel B. Hoyng</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cain, Melinda S" sort="Cain, Melinda S" uniqKey="Cain M" first="Melinda S." last="Cain">Melinda S. Cain</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Richardson, Andrea J" sort="Richardson, Andrea J" uniqKey="Richardson A" first="Andrea J." last="Richardson">Andrea J. Richardson</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Martin, Tammy M" sort="Martin, Tammy M" uniqKey="Martin T" first="Tammy M." last="Martin">Tammy M. Martin</name><affiliation><nlm:aff id="A88">Casey Eye Institute, Oregon Health & Science University, Portland OR, USA</nlm:aff></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation><nlm:aff id="A31">South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E." last="Weeks">Daniel E. Weeks</name><affiliation><nlm:aff id="A32">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Dhillon, Bal" sort="Dhillon, Bal" uniqKey="Dhillon B" first="Bal" last="Dhillon">Bal Dhillon</name><affiliation><nlm:aff id="A90">School of Clinical Sciences University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Doheny, Kimberly F" sort="Doheny, Kimberly F" uniqKey="Doheny K" first="Kimberly F." last="Doheny">Kimberly F. Doheny</name><affiliation><nlm:aff id="A91">Center for Inherited Disease Research (CIDR) Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Romm, Jane" sort="Romm, Jane" uniqKey="Romm J" first="Jane" last="Romm">Jane Romm</name><affiliation><nlm:aff id="A91">Center for Inherited Disease Research (CIDR) Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Klaver, Caroline C W" sort="Klaver, Caroline C W" uniqKey="Klaver C" first="Caroline C. W." last="Klaver">Caroline C. W. Klaver</name><affiliation><nlm:aff id="A34">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A33">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Gorin, Michael B" sort="Gorin, Michael B" uniqKey="Gorin M" first="Michael B." last="Gorin">Michael B. Gorin</name><affiliation><nlm:aff id="A92">Department of Ophthalmology, David Geffen School of Medicine—UCLA, Stein Eye Institute, Los Angeles, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Department of Human Genetics, David Geffen School of Medicine—UCLA, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Michael L" sort="Klein, Michael L" uniqKey="Klein M" first="Michael L." last="Klein">Michael L. Klein</name><affiliation><nlm:aff id="A88">Casey Eye Institute, Oregon Health & Science University, Portland OR, USA</nlm:aff></affiliation></author><author><name sortKey="Baird, Paul N" sort="Baird, Paul N" uniqKey="Baird P" first="Paul N." last="Baird">Paul N. Baird</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Den Hollander, Anneke I" sort="Den Hollander, Anneke I" uniqKey="Den Hollander A" first="Anneke I." last="Den Hollander">Anneke I. Den Hollander</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Fauser, Sascha" sort="Fauser, Sascha" uniqKey="Fauser S" first="Sascha" last="Fauser">Sascha Fauser</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Yates, John R W" sort="Yates, John R W" uniqKey="Yates J" first="John R. W." last="Yates">John R. W. Yates</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Allikmets, Rando" sort="Allikmets, Rando" uniqKey="Allikmets R" first="Rando" last="Allikmets">Rando Allikmets</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Department of Pathology & Cell Biology, Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Schaumberg, Debra A" sort="Schaumberg, Debra A" uniqKey="Schaumberg D" first="Debra A." last="Schaumberg">Debra A. Schaumberg</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Center for Translational Medicine, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Barbara E K" sort="Klein, Barbara E K" uniqKey="Klein B" first="Barbara E. K." last="Klein">Barbara E. K. Klein</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hagstrom, Stephanie A" sort="Hagstrom, Stephanie A" uniqKey="Hagstrom S" first="Stephanie A." last="Hagstrom">Stephanie A. Hagstrom</name><affiliation><nlm:aff id="A77">Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Chowers, Itay" sort="Chowers, Itay" uniqKey="Chowers I" first="Itay" last="Chowers">Itay Chowers</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Lotery, Andrew J" sort="Lotery, Andrew J" uniqKey="Lotery A" first="Andrew J." last="Lotery">Andrew J. Lotery</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Leveillard, Thierry" sort="Leveillard, Thierry" uniqKey="Leveillard T" first="Thierry" last="Léveillard">Thierry Léveillard</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Zhang, Kang" sort="Zhang, Kang" uniqKey="Zhang K" first="Kang" last="Zhang">Kang Zhang</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Brilliant, Murray H" sort="Brilliant, Murray H" uniqKey="Brilliant M" first="Murray H." last="Brilliant">Murray H. Brilliant</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Alex W" sort="Hewitt, Alex W" uniqKey="Hewitt A" first="Alex W." last="Hewitt">Alex W. Hewitt</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Swaroop, Anand" sort="Swaroop, Anand" uniqKey="Swaroop A" first="Anand" last="Swaroop">Anand Swaroop</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Chew, Emily Y" sort="Chew, Emily Y" uniqKey="Chew E" first="Emily Y." last="Chew">Emily Y. Chew</name><affiliation><nlm:aff id="A98">Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A." last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Deangelis, Margaret" sort="Deangelis, Margaret" uniqKey="Deangelis M" first="Margaret" last="Deangelis">Margaret Deangelis</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Stambolian, Dwight" sort="Stambolian, Dwight" uniqKey="Stambolian D" first="Dwight" last="Stambolian">Dwight Stambolian</name><affiliation><nlm:aff id="A10">Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L." last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Iyengar, Sudha K" sort="Iyengar, Sudha K" uniqKey="Iyengar S" first="Sudha K." last="Iyengar">Sudha K. Iyengar</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Weber, Bernhard H F" sort="Weber, Bernhard H F" uniqKey="Weber B" first="Bernhard H. F." last="Weber">Bernhard H. F. Weber</name><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Abecasis, Goncalo R" sort="Abecasis, Goncalo R" uniqKey="Abecasis G" first="Gonçalo R." last="Abecasis">Gonçalo R. Abecasis</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Heid, Iris M" sort="Heid, Iris M" uniqKey="Heid I" first="Iris M." last="Heid">Iris M. Heid</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26691988</idno><idno type="pmc">4745342</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745342</idno><idno type="RBID">PMC:4745342</idno><idno type="doi">10.1038/ng.3448</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002E44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E44</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants</title><author><name sortKey="Fritsche, Lars G" sort="Fritsche, Lars G" uniqKey="Fritsche L" first="Lars G." last="Fritsche">Lars G. Fritsche</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Igl, Wilmar" sort="Igl, Wilmar" uniqKey="Igl W" first="Wilmar" last="Igl">Wilmar Igl</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Cooke Bailey, Jessica N" sort="Cooke Bailey, Jessica N" uniqKey="Cooke Bailey J" first="Jessica N." last="Cooke Bailey">Jessica N. Cooke Bailey</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Grassmann, Felix" sort="Grassmann, Felix" uniqKey="Grassmann F" first="Felix" last="Grassmann">Felix Grassmann</name><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Sengupta, Sebanti" sort="Sengupta, Sebanti" uniqKey="Sengupta S" first="Sebanti" last="Sengupta">Sebanti Sengupta</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Bragg Gresham, Jennifer L" sort="Bragg Gresham, Jennifer L" uniqKey="Bragg Gresham J" first="Jennifer L." last="Bragg-Gresham">Jennifer L. Bragg-Gresham</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Kidney Epidemiology and Cost Center, Department of Internal Medicine - Nephrology, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation></author><author><name sortKey="Burdon, Kathryn P" sort="Burdon, Kathryn P" uniqKey="Burdon K" first="Kathryn P." last="Burdon">Kathryn P. Burdon</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Hebbring, Scott J" sort="Hebbring, Scott J" uniqKey="Hebbring S" first="Scott J." last="Hebbring">Scott J. Hebbring</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Wen, Cindy" sort="Wen, Cindy" uniqKey="Wen C" first="Cindy" last="Wen">Cindy Wen</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Gorski, Mathias" sort="Gorski, Mathias" uniqKey="Gorski M" first="Mathias" last="Gorski">Mathias Gorski</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Kim, Ivana K" sort="Kim, Ivana K" uniqKey="Kim I" first="Ivana K." last="Kim">Ivana K. Kim</name><affiliation><nlm:aff id="A9">Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Cho, David" sort="Cho, David" uniqKey="Cho D" first="David" last="Cho">David Cho</name><affiliation><nlm:aff id="A10">Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Zack, Donald" sort="Zack, Donald" uniqKey="Zack D" first="Donald" last="Zack">Donald Zack</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Molecular Biology and Genetics - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Neuroscience - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institute of Genetic Medicine - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Institue de la Vision, Université Pierre et Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Souied, Eric" sort="Souied, Eric" uniqKey="Souied E" first="Eric" last="Souied">Eric Souied</name><affiliation><nlm:aff id="A16">Hôpital Intercommunal de Créteil, Hôpital Henri Mondor - Université Paris Est Créteil, France</nlm:aff></affiliation></author><author><name sortKey="Scholl, Hendrik P N" sort="Scholl, Hendrik P N" uniqKey="Scholl H" first="Hendrik P. N." last="Scholl">Hendrik P. N. Scholl</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A17">University of Bonn - Department of Ophthalmology, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Bala, Elisa" sort="Bala, Elisa" uniqKey="Bala E" first="Elisa" last="Bala">Elisa Bala</name><affiliation><nlm:aff id="A18">Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Kristine E" sort="Lee, Kristine E" uniqKey="Lee K" first="Kristine E." last="Lee">Kristine E. Lee</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Sardell, Rebecca J" sort="Sardell, Rebecca J" uniqKey="Sardell R" first="Rebecca J." last="Sardell">Rebecca J. Sardell</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Merriam, Joanna E" sort="Merriam, Joanna E" uniqKey="Merriam J" first="Joanna E." last="Merriam">Joanna E. Merriam</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Cipriani, Valentina" sort="Cipriani, Valentina" uniqKey="Cipriani V" first="Valentina" last="Cipriani">Valentina Cipriani</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hoffman, Joshua D" sort="Hoffman, Joshua D" uniqKey="Hoffman J" first="Joshua D." last="Hoffman">Joshua D. Hoffman</name><affiliation><nlm:aff id="A27">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Schick, Tina" sort="Schick, Tina" uniqKey="Schick T" first="Tina" last="Schick">Tina Schick</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Lechanteur, Yara T E" sort="Lechanteur, Yara T E" uniqKey="Lechanteur Y" first="Yara T. E." last="Lechanteur">Yara T. E. Lechanteur</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Guymer, Robyn H" sort="Guymer, Robyn H" uniqKey="Guymer R" first="Robyn H." last="Guymer">Robyn H. Guymer</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Johnson, Matthew P" sort="Johnson, Matthew P" uniqKey="Johnson M" first="Matthew P." last="Johnson">Matthew P. Johnson</name><affiliation><nlm:aff id="A31">South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Jiang, Yingda" sort="Jiang, Yingda" uniqKey="Jiang Y" first="Yingda" last="Jiang">Yingda Jiang</name><affiliation><nlm:aff id="A32">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Stanton, Chloe M" sort="Stanton, Chloe M" uniqKey="Stanton C" first="Chloe M." last="Stanton">Chloe M. Stanton</name><affiliation><nlm:aff id="A33">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Buitendijk, Gabrielle H S" sort="Buitendijk, Gabrielle H S" uniqKey="Buitendijk G" first="Gabriëlle H. S." last="Buitendijk">Gabriëlle H. S. Buitendijk</name><affiliation><nlm:aff id="A34">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhan, Xiaowei" sort="Zhan, Xiaowei" uniqKey="Zhan X" first="Xiaowei" last="Zhan">Xiaowei Zhan</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A36">Quantitative Biomedical Research Center, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Kwong, Alan M" sort="Kwong, Alan M" uniqKey="Kwong A" first="Alan M." last="Kwong">Alan M. Kwong</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Boleda, Alexis" sort="Boleda, Alexis" uniqKey="Boleda A" first="Alexis" last="Boleda">Alexis Boleda</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Brooks, Matthew" sort="Brooks, Matthew" uniqKey="Brooks M" first="Matthew" last="Brooks">Matthew Brooks</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Gieser, Linn" sort="Gieser, Linn" uniqKey="Gieser L" first="Linn" last="Gieser">Linn Gieser</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Ratnapriya, Rinki" sort="Ratnapriya, Rinki" uniqKey="Ratnapriya R" first="Rinki" last="Ratnapriya">Rinki Ratnapriya</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Branham, Kari E" sort="Branham, Kari E" uniqKey="Branham K" first="Kari E." last="Branham">Kari E. Branham</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Foerster, Johanna R" sort="Foerster, Johanna R" uniqKey="Foerster J" first="Johanna R." last="Foerster">Johanna R. Foerster</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Heckenlively, John R" sort="Heckenlively, John R" uniqKey="Heckenlively J" first="John R." last="Heckenlively">John R. Heckenlively</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Othman, Mohammad I" sort="Othman, Mohammad I" uniqKey="Othman M" first="Mohammad I." last="Othman">Mohammad I. Othman</name><affiliation><nlm:aff id="A39">Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Vote, Brendan J" sort="Vote, Brendan J" uniqKey="Vote B" first="Brendan J." last="Vote">Brendan J. Vote</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Liang, Helena Hai" sort="Liang, Helena Hai" uniqKey="Liang H" first="Helena Hai" last="Liang">Helena Hai Liang</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Souzeau, Emmanuelle" sort="Souzeau, Emmanuelle" uniqKey="Souzeau E" first="Emmanuelle" last="Souzeau">Emmanuelle Souzeau</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcallister, Ian L" sort="Mcallister, Ian L" uniqKey="Mcallister I" first="Ian L." last="Mcallister">Ian L. Mcallister</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Timothy" sort="Isaacs, Timothy" uniqKey="Isaacs T" first="Timothy" last="Isaacs">Timothy Isaacs</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Hall, Janette" sort="Hall, Janette" uniqKey="Hall J" first="Janette" last="Hall">Janette Hall</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Lake, Stewart" sort="Lake, Stewart" uniqKey="Lake S" first="Stewart" last="Lake">Stewart Lake</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Mackey, David A" sort="Mackey, David A" uniqKey="Mackey D" first="David A." last="Mackey">David A. Mackey</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Constable, Ian J" sort="Constable, Ian J" uniqKey="Constable I" first="Ian J." last="Constable">Ian J. Constable</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Craig, Jamie E" sort="Craig, Jamie E" uniqKey="Craig J" first="Jamie E." last="Craig">Jamie E. Craig</name><affiliation><nlm:aff id="A40">Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Kitchner, Terrie E" sort="Kitchner, Terrie E" uniqKey="Kitchner T" first="Terrie E." last="Kitchner">Terrie E. Kitchner</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Yang, Zhenglin" sort="Yang, Zhenglin" uniqKey="Yang Z" first="Zhenglin" last="Yang">Zhenglin Yang</name><affiliation><nlm:aff id="A42">Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China</nlm:aff></affiliation></author><author><name sortKey="Su, Zhiguang" sort="Su, Zhiguang" uniqKey="Su Z" first="Zhiguang" last="Su">Zhiguang Su</name><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Luo, Hongrong" sort="Luo, Hongrong" uniqKey="Luo H" first="Hongrong" last="Luo">Hongrong Luo</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Chen, Daniel" sort="Chen, Daniel" uniqKey="Chen D" first="Daniel" last="Chen">Daniel Chen</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ouyang, Hong" sort="Ouyang, Hong" uniqKey="Ouyang H" first="Hong" last="Ouyang">Hong Ouyang</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Flagg, Ken" sort="Flagg, Ken" uniqKey="Flagg K" first="Ken" last="Flagg">Ken Flagg</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Lin, Danni" sort="Lin, Danni" uniqKey="Lin D" first="Danni" last="Lin">Danni Lin</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Mao, Guanping" sort="Mao, Guanping" uniqKey="Mao G" first="Guanping" last="Mao">Guanping Mao</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Ferreyra, Henry" sort="Ferreyra, Henry" uniqKey="Ferreyra H" first="Henry" last="Ferreyra">Henry Ferreyra</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Stark, Klaus" sort="Stark, Klaus" uniqKey="Stark K" first="Klaus" last="Stark">Klaus Stark</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Von Strachwitz, Claudia N" sort="Von Strachwitz, Claudia N" uniqKey="Von Strachwitz C" first="Claudia N." last="Von Strachwitz">Claudia N. Von Strachwitz</name><affiliation><nlm:aff id="A45">EyeCentre Southwest, Stuttgart, Baden-Württemberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolf, Armin" sort="Wolf, Armin" uniqKey="Wolf A" first="Armin" last="Wolf">Armin Wolf</name><affiliation><nlm:aff id="A46">University Eye Clinic, Ludwig-Maximilians-University, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Brandl, Caroline" sort="Brandl, Caroline" uniqKey="Brandl C" first="Caroline" last="Brandl">Caroline Brandl</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A47">Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Rudolph, Guenther" sort="Rudolph, Guenther" uniqKey="Rudolph G" first="Guenther" last="Rudolph">Guenther Rudolph</name><affiliation><nlm:aff id="A46">University Eye Clinic, Ludwig-Maximilians-University, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Olden, Matthias" sort="Olden, Matthias" uniqKey="Olden M" first="Matthias" last="Olden">Matthias Olden</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Morrison, Margaux A" sort="Morrison, Margaux A" uniqKey="Morrison M" first="Margaux A." last="Morrison">Margaux A. Morrison</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Morgan, Denise J" sort="Morgan, Denise J" uniqKey="Morgan D" first="Denise J." last="Morgan">Denise J. Morgan</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Schu, Matthew" sort="Schu, Matthew" uniqKey="Schu M" first="Matthew" last="Schu">Matthew Schu</name><affiliation><nlm:aff id="A49">Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Ahn, Jeeyun" sort="Ahn, Jeeyun" uniqKey="Ahn J" first="Jeeyun" last="Ahn">Jeeyun Ahn</name><affiliation><nlm:aff id="A54">Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Silvestri, Giuliana" sort="Silvestri, Giuliana" uniqKey="Silvestri G" first="Giuliana" last="Silvestri">Giuliana Silvestri</name><affiliation><nlm:aff id="A55">Centre for Experimental Medicine, Queen's University, Belfast, UK</nlm:aff></affiliation></author><author><name sortKey="Tsironi, Evangelia E" sort="Tsironi, Evangelia E" uniqKey="Tsironi E" first="Evangelia E." last="Tsironi">Evangelia E. Tsironi</name><affiliation><nlm:aff id="A56">Department of Ophthalmology, University of Thessaly, School of Medicine, Larissa, Greece</nlm:aff></affiliation></author><author><name sortKey="Park, Kyu Hyung" sort="Park, Kyu Hyung" uniqKey="Park K" first="Kyu Hyung" last="Park">Kyu Hyung Park</name><affiliation><nlm:aff id="A57">Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea</nlm:aff></affiliation></author><author><name sortKey="Farrer, Lindsay A" sort="Farrer, Lindsay A" uniqKey="Farrer L" first="Lindsay A." last="Farrer">Lindsay A. Farrer</name><affiliation><nlm:aff id="A49">Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A50">Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A51">Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Orlin, Anton" sort="Orlin, Anton" uniqKey="Orlin A" first="Anton" last="Orlin">Anton Orlin</name><affiliation><nlm:aff id="A58">Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Brucker, Alexander" sort="Brucker, Alexander" uniqKey="Brucker A" first="Alexander" last="Brucker">Alexander Brucker</name><affiliation><nlm:aff id="A59">Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Mingyao" sort="Li, Mingyao" uniqKey="Li M" first="Mingyao" last="Li">Mingyao Li</name><affiliation><nlm:aff id="A60">Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Curcio, Christine" sort="Curcio, Christine" uniqKey="Curcio C" first="Christine" last="Curcio">Christine Curcio</name><affiliation><nlm:aff id="A61">Department of Ophthalmology, The University of Alabama at Birmingham, Birmingham, AL, USA</nlm:aff></affiliation></author><author><name sortKey="Mohand Said, Saddek" sort="Mohand Said, Saddek" uniqKey="Mohand Said S" first="Saddek" last="Mohand-Saïd">Saddek Mohand-Saïd</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Sahel, Jose Alain" sort="Sahel, Jose Alain" uniqKey="Sahel J" first="José-Alain" last="Sahel">José-Alain Sahel</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Fondation Ophtalmologique Adolphe de Rothschild, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Académie des Sciences–Institut de France, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Audo, Isabelle" sort="Audo, Isabelle" uniqKey="Audo I" first="Isabelle" last="Audo">Isabelle Audo</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A68">Department of Molecular Genetics, Institute of Ophthalmology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Benchaboune, Mustapha" sort="Benchaboune, Mustapha" uniqKey="Benchaboune M" first="Mustapha" last="Benchaboune">Mustapha Benchaboune</name><affiliation><nlm:aff id="A65">Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Cree, Angela J" sort="Cree, Angela J" uniqKey="Cree A" first="Angela J." last="Cree">Angela J. Cree</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Rennie, Christina A" sort="Rennie, Christina A" uniqKey="Rennie C" first="Christina A." last="Rennie">Christina A. Rennie</name><affiliation><nlm:aff id="A70">University Hospital Southampton, Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Goverdhan, Srinivas V" sort="Goverdhan, Srinivas V" uniqKey="Goverdhan S" first="Srinivas V." last="Goverdhan">Srinivas V. Goverdhan</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Grunin, Michelle" sort="Grunin, Michelle" uniqKey="Grunin M" first="Michelle" last="Grunin">Michelle Grunin</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Hagbi Levi, Shira" sort="Hagbi Levi, Shira" uniqKey="Hagbi Levi S" first="Shira" last="Hagbi-Levi">Shira Hagbi-Levi</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Campochiaro, Peter" sort="Campochiaro, Peter" uniqKey="Campochiaro P" first="Peter" last="Campochiaro">Peter Campochiaro</name><affiliation><nlm:aff id="A11">Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Neuroscience - Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Katsanis, Nicholas" sort="Katsanis, Nicholas" uniqKey="Katsanis N" first="Nicholas" last="Katsanis">Nicholas Katsanis</name><affiliation><nlm:aff id="A72">Center for Human Disease Modeling, Duke University, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A73">Department of Cell Biology, Duke University, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A74">Department of Pediatrics, Duke University, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Holz, Frank G" sort="Holz, Frank G" uniqKey="Holz F" first="Frank G." last="Holz">Frank G. Holz</name><affiliation><nlm:aff id="A17">University of Bonn - Department of Ophthalmology, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Blond, Frederic" sort="Blond, Frederic" uniqKey="Blond F" first="Frédéric" last="Blond">Frédéric Blond</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Blanche, Helene" sort="Blanche, Helene" uniqKey="Blanche H" first="Hélène" last="Blanché">Hélène Blanché</name><affiliation><nlm:aff id="A75">CEPH Fondation Jean Dausset Paris, France</nlm:aff></affiliation></author><author><name sortKey="Deleuze, Jean Francois" sort="Deleuze, Jean Francois" uniqKey="Deleuze J" first="Jean-François" last="Deleuze">Jean-François Deleuze</name><affiliation><nlm:aff id="A75">CEPH Fondation Jean Dausset Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A76">CEA – IG – Centre National de Génotypage Evry Cédex, France</nlm:aff></affiliation></author><author><name sortKey="Igo, Robert P" sort="Igo, Robert P" uniqKey="Igo R" first="Robert P." last="Igo">Robert P. Igo</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Truitt, Barbara" sort="Truitt, Barbara" uniqKey="Truitt B" first="Barbara" last="Truitt">Barbara Truitt</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Peachey, Neal S" sort="Peachey, Neal S" uniqKey="Peachey N" first="Neal S." last="Peachey">Neal S. Peachey</name><affiliation><nlm:aff id="A18">Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A77">Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Meuer, Stacy M" sort="Meuer, Stacy M" uniqKey="Meuer S" first="Stacy M." last="Meuer">Stacy M. Meuer</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Myers, Chelsea E" sort="Myers, Chelsea E" uniqKey="Myers C" first="Chelsea E." last="Myers">Chelsea E. Myers</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Moore, Emily L" sort="Moore, Emily L" uniqKey="Moore E" first="Emily L." last="Moore">Emily L. Moore</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Ronald" sort="Klein, Ronald" uniqKey="Klein R" first="Ronald" last="Klein">Ronald Klein</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><affiliation><nlm:aff id="A78">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A79">Department of Medicine, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Postel, Eric A" sort="Postel, Eric A" uniqKey="Postel E" first="Eric A." last="Postel">Eric A. Postel</name><affiliation><nlm:aff id="A78">Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Courtenay, Monique D" sort="Courtenay, Monique D" uniqKey="Courtenay M" first="Monique D." last="Courtenay">Monique D. Courtenay</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Schwartz, Stephen G" sort="Schwartz, Stephen G" uniqKey="Schwartz S" first="Stephen G." last="Schwartz">Stephen G. Schwartz</name><affiliation><nlm:aff id="A81">Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Kovach, Jaclyn L" sort="Kovach, Jaclyn L" uniqKey="Kovach J" first="Jaclyn L." last="Kovach">Jaclyn L. Kovach</name><affiliation><nlm:aff id="A81">Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Liew, Gerald" sort="Liew, Gerald" uniqKey="Liew G" first="Gerald" last="Liew">Gerald Liew</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="T An, Ava G" sort="T An, Ava G" uniqKey="T An A" first="Ava G." last="T An">Ava G. T An</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Gopinath, Bamini" sort="Gopinath, Bamini" uniqKey="Gopinath B" first="Bamini" last="Gopinath">Bamini Gopinath</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Merriam, John C" sort="Merriam, John C" uniqKey="Merriam J" first="John C." last="Merriam">John C. Merriam</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Smith, R Theodore" sort="Smith, R Theodore" uniqKey="Smith R" first="R. Theodore" last="Smith">R. Theodore Smith</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Ophthalmology, NYU School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Khan, Jane C" sort="Khan, Jane C" uniqKey="Khan J" first="Jane C." last="Khan">Jane C. Khan</name><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A83">Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Shahid, Humma" sort="Shahid, Humma" uniqKey="Shahid H" first="Humma" last="Shahid">Humma Shahid</name><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A85">Department of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Moore, Anthony T" sort="Moore, Anthony T" uniqKey="Moore A" first="Anthony T." last="Moore">Anthony T. Moore</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Department of Ophthalmology UCSF Medical School, San Francisco, CA USA</nlm:aff></affiliation></author><author><name sortKey="Mcgrath, J Allie" sort="Mcgrath, J Allie" uniqKey="Mcgrath J" first="J. Allie" last="Mcgrath">J. Allie Mcgrath</name><affiliation><nlm:aff id="A27">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Laux, Renee" sort="Laux, Renee" uniqKey="Laux R" first="Reneé" last="Laux">Reneé Laux</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Brantley, Milam A" sort="Brantley, Milam A" uniqKey="Brantley M" first="Milam A." last="Brantley">Milam A. Brantley</name><affiliation><nlm:aff id="A87">Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Agarwal, Anita" sort="Agarwal, Anita" uniqKey="Agarwal A" first="Anita" last="Agarwal">Anita Agarwal</name><affiliation><nlm:aff id="A87">Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Ersoy, Lebriz" sort="Ersoy, Lebriz" uniqKey="Ersoy L" first="Lebriz" last="Ersoy">Lebriz Ersoy</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Caramoy, Albert" sort="Caramoy, Albert" uniqKey="Caramoy A" first="Albert" last="Caramoy">Albert Caramoy</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Langmann, Thomas" sort="Langmann, Thomas" uniqKey="Langmann T" first="Thomas" last="Langmann">Thomas Langmann</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Saksens, Nicole T M" sort="Saksens, Nicole T M" uniqKey="Saksens N" first="Nicole T. M." last="Saksens">Nicole T. M. Saksens</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Jong, Eiko K" sort="De Jong, Eiko K" uniqKey="De Jong E" first="Eiko K." last="De Jong">Eiko K. De Jong</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hoyng, Carel B" sort="Hoyng, Carel B" uniqKey="Hoyng C" first="Carel B." last="Hoyng">Carel B. Hoyng</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cain, Melinda S" sort="Cain, Melinda S" uniqKey="Cain M" first="Melinda S." last="Cain">Melinda S. Cain</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Richardson, Andrea J" sort="Richardson, Andrea J" uniqKey="Richardson A" first="Andrea J." last="Richardson">Andrea J. Richardson</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Martin, Tammy M" sort="Martin, Tammy M" uniqKey="Martin T" first="Tammy M." last="Martin">Tammy M. Martin</name><affiliation><nlm:aff id="A88">Casey Eye Institute, Oregon Health & Science University, Portland OR, USA</nlm:aff></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation><nlm:aff id="A31">South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E." last="Weeks">Daniel E. Weeks</name><affiliation><nlm:aff id="A32">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A89">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Dhillon, Bal" sort="Dhillon, Bal" uniqKey="Dhillon B" first="Bal" last="Dhillon">Bal Dhillon</name><affiliation><nlm:aff id="A90">School of Clinical Sciences University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Doheny, Kimberly F" sort="Doheny, Kimberly F" uniqKey="Doheny K" first="Kimberly F." last="Doheny">Kimberly F. Doheny</name><affiliation><nlm:aff id="A91">Center for Inherited Disease Research (CIDR) Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Romm, Jane" sort="Romm, Jane" uniqKey="Romm J" first="Jane" last="Romm">Jane Romm</name><affiliation><nlm:aff id="A91">Center for Inherited Disease Research (CIDR) Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Klaver, Caroline C W" sort="Klaver, Caroline C W" uniqKey="Klaver C" first="Caroline C. W." last="Klaver">Caroline C. W. Klaver</name><affiliation><nlm:aff id="A34">Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation><nlm:aff id="A33">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK</nlm:aff></affiliation></author><author><name sortKey="Gorin, Michael B" sort="Gorin, Michael B" uniqKey="Gorin M" first="Michael B." last="Gorin">Michael B. Gorin</name><affiliation><nlm:aff id="A92">Department of Ophthalmology, David Geffen School of Medicine—UCLA, Stein Eye Institute, Los Angeles, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Department of Human Genetics, David Geffen School of Medicine—UCLA, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Michael L" sort="Klein, Michael L" uniqKey="Klein M" first="Michael L." last="Klein">Michael L. Klein</name><affiliation><nlm:aff id="A88">Casey Eye Institute, Oregon Health & Science University, Portland OR, USA</nlm:aff></affiliation></author><author><name sortKey="Baird, Paul N" sort="Baird, Paul N" uniqKey="Baird P" first="Paul N." last="Baird">Paul N. Baird</name><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Den Hollander, Anneke I" sort="Den Hollander, Anneke I" uniqKey="Den Hollander A" first="Anneke I." last="Den Hollander">Anneke I. Den Hollander</name><affiliation><nlm:aff id="A29">Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Fauser, Sascha" sort="Fauser, Sascha" uniqKey="Fauser S" first="Sascha" last="Fauser">Sascha Fauser</name><affiliation><nlm:aff id="A28">University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Yates, John R W" sort="Yates, John R W" uniqKey="Yates J" first="John R. W." last="Yates">John R. W. Yates</name><affiliation><nlm:aff id="A25">UCL Institute of Ophthalmology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Moorfields Eye Hospital, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A84">Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Allikmets, Rando" sort="Allikmets, Rando" uniqKey="Allikmets R" first="Rando" last="Allikmets">Rando Allikmets</name><affiliation><nlm:aff id="A24">Department of Ophthalmology Columbia University, New York, NY, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Department of Pathology & Cell Biology, Columbia University, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="A23">Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Schaumberg, Debra A" sort="Schaumberg, Debra A" uniqKey="Schaumberg D" first="Debra A." last="Schaumberg">Debra A. Schaumberg</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Center for Translational Medicine, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Klein, Barbara E K" sort="Klein, Barbara E K" uniqKey="Klein B" first="Barbara E. K." last="Klein">Barbara E. K. Klein</name><affiliation><nlm:aff id="A19">Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hagstrom, Stephanie A" sort="Hagstrom, Stephanie A" uniqKey="Hagstrom S" first="Stephanie A." last="Hagstrom">Stephanie A. Hagstrom</name><affiliation><nlm:aff id="A77">Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Chowers, Itay" sort="Chowers, Itay" uniqKey="Chowers I" first="Itay" last="Chowers">Itay Chowers</name><affiliation><nlm:aff id="A71">Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</nlm:aff></affiliation></author><author><name sortKey="Lotery, Andrew J" sort="Lotery, Andrew J" uniqKey="Lotery A" first="Andrew J." last="Lotery">Andrew J. Lotery</name><affiliation><nlm:aff id="A69">Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</nlm:aff></affiliation></author><author><name sortKey="Leveillard, Thierry" sort="Leveillard, Thierry" uniqKey="Leveillard T" first="Thierry" last="Léveillard">Thierry Léveillard</name><affiliation><nlm:aff id="A62">INSERM, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A63">Institut de la Vision, Department of Genetics, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A64">CNRS, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Zhang, Kang" sort="Zhang, Kang" uniqKey="Zhang K" first="Kang" last="Zhang">Kang Zhang</name><affiliation><nlm:aff id="A8">Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</nlm:aff></affiliation></author><author><name sortKey="Brilliant, Murray H" sort="Brilliant, Murray H" uniqKey="Brilliant M" first="Murray H." last="Brilliant">Murray H. Brilliant</name><affiliation><nlm:aff id="A7">Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Alex W" sort="Hewitt, Alex W" uniqKey="Hewitt A" first="Alex W." last="Hewitt">Alex W. Hewitt</name><affiliation><nlm:aff id="A6">School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A41">Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</nlm:aff></affiliation></author><author><name sortKey="Swaroop, Anand" sort="Swaroop, Anand" uniqKey="Swaroop A" first="Anand" last="Swaroop">Anand Swaroop</name><affiliation><nlm:aff id="A38">Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Chew, Emily Y" sort="Chew, Emily Y" uniqKey="Chew E" first="Emily Y." last="Chew">Emily Y. Chew</name><affiliation><nlm:aff id="A98">Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret A." last="Pericak-Vance">Margaret A. Pericak-Vance</name><affiliation><nlm:aff id="A22">John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Deangelis, Margaret" sort="Deangelis, Margaret" uniqKey="Deangelis M" first="Margaret" last="Deangelis">Margaret Deangelis</name><affiliation><nlm:aff id="A48">Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</nlm:aff></affiliation></author><author><name sortKey="Stambolian, Dwight" sort="Stambolian, Dwight" uniqKey="Stambolian D" first="Dwight" last="Stambolian">Dwight Stambolian</name><affiliation><nlm:aff id="A10">Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</nlm:aff></affiliation></author><author><name sortKey="Haines, Jonathan L" sort="Haines, Jonathan L" uniqKey="Haines J" first="Jonathan L." last="Haines">Jonathan L. Haines</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Iyengar, Sudha K" sort="Iyengar, Sudha K" uniqKey="Iyengar S" first="Sudha K." last="Iyengar">Sudha K. Iyengar</name><affiliation><nlm:aff id="A3">Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</nlm:aff></affiliation></author><author><name sortKey="Weber, Bernhard H F" sort="Weber, Bernhard H F" uniqKey="Weber B" first="Bernhard H. F." last="Weber">Bernhard H. F. Weber</name><affiliation><nlm:aff id="A4">Institute of Human Genetics, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Abecasis, Goncalo R" sort="Abecasis, Goncalo R" uniqKey="Abecasis G" first="Gonçalo R." last="Abecasis">Gonçalo R. Abecasis</name><affiliation><nlm:aff id="A1">Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Heid, Iris M" sort="Heid, Iris M" uniqKey="Heid I" first="Iris M." last="Heid">Iris M. Heid</name><affiliation><nlm:aff id="A2">Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</nlm:aff></affiliation></author></analytic><series><title level="j">Nature genetics</title><idno type="ISSN">1061-4036</idno><idno type="eISSN">1546-1718</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10<sup>–8</sup>) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near <italic>MMP9</italic> (difference-P = 4.1×10<sup>–10</sup>). Very rare coding variants (frequency < 0.1%) in <italic>CFH</italic>, <italic>CFI</italic>, and <italic>TIMP3</italic> suggest causal roles for these genes, as does a splice variant in <italic>SLC16A8</italic>. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Smith, W" uniqKey="Smith W">W Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chakravarthy, U" uniqKey="Chakravarthy U">U Chakravarthy</name></author><author><name sortKey="Evans, J" uniqKey="Evans J">J Evans</name></author><author><name sortKey="Rosenfeld, Pj" uniqKey="Rosenfeld P">PJ Rosenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferris, Fl" uniqKey="Ferris F">FL Ferris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wong, Wl" uniqKey="Wong W">WL Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fritsche, Lg" uniqKey="Fritsche L">LG Fritsche</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fritsche, Lg" uniqKey="Fritsche L">LG Fritsche</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raychaudhuri, S" uniqKey="Raychaudhuri S">S Raychaudhuri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Helgason, H" uniqKey="Helgason H">H Helgason</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seddon, Jm" uniqKey="Seddon J">JM Seddon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhan, X" uniqKey="Zhan X">X Zhan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Ven, Jp" uniqKey="Van De Ven J">JP van de Ven</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arakawa, S" uniqKey="Arakawa S">S Arakawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gibson, G" uniqKey="Gibson G">G Gibson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Do, R" uniqKey="Do R">R Do</name></author><author><name sortKey="Kathiresan, S" uniqKey="Kathiresan S">S Kathiresan</name></author><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Mr" uniqKey="Nelson M">MR Nelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zuk, O" uniqKey="Zuk O">O Zuk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vogelstein, B" uniqKey="Vogelstein B">B Vogelstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rivas, Ma" uniqKey="Rivas M">MA Rivas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flannick, J" uniqKey="Flannick J">J Flannick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruchaga, C" uniqKey="Cruchaga C">C Cruchaga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Do, R" uniqKey="Do R">R Do</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lange, La" uniqKey="Lange L">LA Lange</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walters, Rg" uniqKey="Walters R">RG Walters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Locke, Ae" uniqKey="Locke A">AE Locke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shungin, D" uniqKey="Shungin D">D Shungin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Lee, Sh" uniqKey="Lee S">SH Lee</name></author><author><name sortKey="Goddard, Me" uniqKey="Goddard M">ME Goddard</name></author><author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Sh" uniqKey="Lee S">SH Lee</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Goddard, Me" uniqKey="Goddard M">ME Goddard</name></author><author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name></author><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wen, X" uniqKey="Wen X">X Wen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nejentsev, S" uniqKey="Nejentsev S">S Nejentsev</name></author><author><name sortKey="Walker, N" uniqKey="Walker N">N Walker</name></author><author><name sortKey="Riches, D" uniqKey="Riches D">D Riches</name></author><author><name sortKey="Egholm, M" uniqKey="Egholm M">M Egholm</name></author><author><name sortKey="Todd, Ja" uniqKey="Todd J">JA Todd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sorsby, A" uniqKey="Sorsby A">A Sorsby</name></author><author><name sortKey="Mason, Me" uniqKey="Mason M">ME Mason</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weber, Bh" uniqKey="Weber B">BH Weber</name></author><author><name sortKey="Vogt, G" uniqKey="Vogt G">G Vogt</name></author><author><name sortKey="Wolz, W" uniqKey="Wolz W">W Wolz</name></author><author><name sortKey="Ives, Ej" uniqKey="Ives E">EJ Ives</name></author><author><name sortKey="Ewing, Cc" uniqKey="Ewing C">CC Ewing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Speliotes, Ek" uniqKey="Speliotes E">EK Speliotes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kottgen, A" uniqKey="Kottgen A">A Kottgen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allikmets, R" uniqKey="Allikmets R">R Allikmets</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Halestrap, Ap" uniqKey="Halestrap A">AP Halestrap</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Daniele, Ll" uniqKey="Daniele L">LL Daniele</name></author><author><name sortKey="Sauer, B" uniqKey="Sauer B">B Sauer</name></author><author><name sortKey="Gallagher, Sm" uniqKey="Gallagher S">SM Gallagher</name></author><author><name sortKey="Pugh, En" uniqKey="Pugh E">EN Pugh</name></author><author><name sortKey="Philp, Nj" uniqKey="Philp N">NJ Philp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shoshan, V" uniqKey="Shoshan V">V Shoshan</name></author><author><name sortKey="Maclennan, Dh" uniqKey="Maclennan D">DH MacLennan</name></author><author><name sortKey="Wood, Ds" uniqKey="Wood D">DS Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stranger, Be" uniqKey="Stranger B">BE Stranger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, C" uniqKey="Lambert C">C Lambert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hollborn, M" uniqKey="Hollborn M">M Hollborn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rudnicka, Ar" uniqKey="Rudnicka A">AR Rudnicka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, W" uniqKey="Chen W">W Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Logue, Mw" uniqKey="Logue M">MW Logue</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hussain, Aa" uniqKey="Hussain A">AA Hussain</name></author><author><name sortKey="Lee, Y" uniqKey="Lee Y">Y Lee</name></author><author><name sortKey="Zhang, Jj" uniqKey="Zhang J">JJ Zhang</name></author><author><name sortKey="Marshall, J" uniqKey="Marshall J">J Marshall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansen, Ct" uniqKey="Johansen C">CT Johansen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Price, Al" uniqKey="Price A">AL Price</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Barrett, Jc" uniqKey="Barrett J">JC Barrett</name></author><author><name sortKey="Fry, B" uniqKey="Fry B">B Fry</name></author><author><name sortKey="Maller, J" uniqKey="Maller J">J Maller</name></author><author><name sortKey="Daly, Mj" uniqKey="Daly M">MJ Daly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sherry, St" uniqKey="Sherry S">ST Sherry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tennessen, Ja" uniqKey="Tennessen J">JA Tennessen</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Fritsche, Lg" uniqKey="Fritsche L">LG Fritsche</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pruitt, Kd" uniqKey="Pruitt K">KD Pruitt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Sb" uniqKey="Ng S">SB Ng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wildeman, M" uniqKey="Wildeman M">M Wildeman</name></author><author><name sortKey="Van Ophuizen, E" uniqKey="Van Ophuizen E">E van Ophuizen</name></author><author><name sortKey="Den Dunnen, Jt" uniqKey="Den Dunnen J">JT den Dunnen</name></author><author><name sortKey="Taschner, Pe" uniqKey="Taschner P">PE Taschner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delaneau, O" uniqKey="Delaneau O">O Delaneau</name></author><author><name sortKey="Marchini, J" uniqKey="Marchini J">J Marchini</name></author><author><name sortKey="Zagury, Jf" uniqKey="Zagury J">JF Zagury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ristau, T" uniqKey="Ristau T">T Ristau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Howie, B" uniqKey="Howie B">B Howie</name></author><author><name sortKey="Fuchsberger, C" uniqKey="Fuchsberger C">C Fuchsberger</name></author><author><name sortKey="Stephens, M" uniqKey="Stephens M">M Stephens</name></author><author><name sortKey="Marchini, J" uniqKey="Marchini J">J Marchini</name></author><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manichaikul, A" uniqKey="Manichaikul A">A Manichaikul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turner, S" uniqKey="Turner S">S Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cavalli Sforza, Ll" uniqKey="Cavalli Sforza L">LL Cavalli-Sforza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Sh" uniqKey="Lee S">SH Lee</name></author><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name></author><author><name sortKey="Goddard, Me" uniqKey="Goddard M">ME Goddard</name></author><author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Firth, D" uniqKey="Firth D">D Firth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author><author><name sortKey="Blackwell, T" uniqKey="Blackwell T">T Blackwell</name></author><author><name sortKey="Boehnke, M" uniqKey="Boehnke M">M Boehnke</name></author><author><name sortKey="Scott, Lj" uniqKey="Scott L">LJ Scott</name></author><author><name sortKey="Go, Tdi" uniqKey="Go T">TDi Go</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devlin, B" uniqKey="Devlin B">B Devlin</name></author><author><name sortKey="Roeder, K" uniqKey="Roeder K">K Roeder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stephens, M" uniqKey="Stephens M">M Stephens</name></author><author><name sortKey="Balding, Dj" uniqKey="Balding D">DJ Balding</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Blake, Ja" uniqKey="Blake J">JA Blake</name></author><author><name sortKey="Bult, Cj" uniqKey="Bult C">CJ Bult</name></author><author><name sortKey="Eppig, Jt" uniqKey="Eppig J">JT Eppig</name></author><author><name sortKey="Kadin, Ja" uniqKey="Kadin J">JA Kadin</name></author><author><name sortKey="Richardson, Je" uniqKey="Richardson J">JE Richardson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, Sd" uniqKey="Brown S">SD Brown</name></author><author><name sortKey="Moore, Mw" uniqKey="Moore M">MW Moore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Ph" uniqKey="Lee P">PH Lee</name></author><author><name sortKey="O Dushlaine, C" uniqKey="O Dushlaine C">C O'Dushlaine</name></author><author><name sortKey="Thomas, B" uniqKey="Thomas B">B Thomas</name></author><author><name sortKey="Purcell, Sm" uniqKey="Purcell S">SM Purcell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanehisa, M" uniqKey="Kanehisa M">M Kanehisa</name></author><author><name sortKey="Goto, S" uniqKey="Goto S">S Goto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Croft, D" uniqKey="Croft D">D Croft</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashburner, M" uniqKey="Ashburner M">M Ashburner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Law, V" uniqKey="Law V">V Law</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="So, Hc" uniqKey="So H">HC So</name></author><author><name sortKey="Gui, Ah" uniqKey="Gui A">AH Gui</name></author><author><name sortKey="Cherny, Ss" uniqKey="Cherny S">SS Cherny</name></author><author><name sortKey="Sham, Pc" uniqKey="Sham P">PC Sham</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9216904</journal-id><journal-id journal-id-type="pubmed-jr-id">2419</journal-id><journal-id journal-id-type="nlm-ta">Nat Genet</journal-id><journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id><journal-title-group><journal-title>Nature genetics</journal-title></journal-title-group><issn pub-type="ppub">1061-4036</issn><issn pub-type="epub">1546-1718</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26691988</article-id><article-id pub-id-type="pmc">4745342</article-id><article-id pub-id-type="doi">10.1038/ng.3448</article-id><article-id pub-id-type="manuscript">NIHMS733253</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fritsche</surname><given-names>Lars G.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Igl</surname><given-names>Wilmar</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Cooke Bailey</surname><given-names>Jessica N.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Grassmann</surname><given-names>Felix</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Sengupta</surname><given-names>Sebanti</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Bragg-Gresham</surname><given-names>Jennifer L.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Burdon</surname><given-names>Kathryn P.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Hebbring</surname><given-names>Scott J.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Wen</surname><given-names>Cindy</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Gorski</surname><given-names>Mathias</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Ivana K.</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Zack</surname><given-names>Donald</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Souied</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Scholl</surname><given-names>Hendrik P. N.</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Bala</surname><given-names>Elisa</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Kristine E.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Hunter</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="A20">20</xref><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Sardell</surname><given-names>Rebecca J.</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Mitchell</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Merriam</surname><given-names>Joanna E.</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Cipriani</surname><given-names>Valentina</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Hoffman</surname><given-names>Joshua D.</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Schick</surname><given-names>Tina</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Lechanteur</surname><given-names>Yara T. E.</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Guymer</surname><given-names>Robyn H.</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Matthew P.</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Yingda</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Stanton</surname><given-names>Chloe M.</given-names></name><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Buitendijk</surname><given-names>Gabriëlle H. S.</given-names></name><xref ref-type="aff" rid="A34">34</xref><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Zhan</surname><given-names>Xiaowei</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A36">36</xref><xref ref-type="aff" rid="A37">37</xref></contrib><contrib contrib-type="author"><name><surname>Kwong</surname><given-names>Alan M.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Boleda</surname><given-names>Alexis</given-names></name><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Brooks</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Gieser</surname><given-names>Linn</given-names></name><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Ratnapriya</surname><given-names>Rinki</given-names></name><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Branham</surname><given-names>Kari E.</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Foerster</surname><given-names>Johanna R.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Heckenlively</surname><given-names>John R.</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Othman</surname><given-names>Mohammad I.</given-names></name><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Vote</surname><given-names>Brendan J.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Liang</surname><given-names>Helena Hai</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Souzeau</surname><given-names>Emmanuelle</given-names></name><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>McAllister</surname><given-names>Ian L.</given-names></name><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Isaacs</surname><given-names>Timothy</given-names></name><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Hall</surname><given-names>Janette</given-names></name><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Lake</surname><given-names>Stewart</given-names></name><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Mackey</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A30">30</xref><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Constable</surname><given-names>Ian J.</given-names></name><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Craig</surname><given-names>Jamie E.</given-names></name><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Kitchner</surname><given-names>Terrie E.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Zhenglin</given-names></name><xref ref-type="aff" rid="A42">42</xref><xref ref-type="aff" rid="A43">43</xref></contrib><contrib contrib-type="author"><name><surname>Su</surname><given-names>Zhiguang</given-names></name><xref ref-type="aff" rid="A44">44</xref></contrib><contrib contrib-type="author"><name><surname>Luo</surname><given-names>Hongrong</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A44">44</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Ouyang</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Flagg</surname><given-names>Ken</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Danni</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Mao</surname><given-names>Guanping</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Ferreyra</surname><given-names>Henry</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Stark</surname><given-names>Klaus</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>von Strachwitz</surname><given-names>Claudia N.</given-names></name><xref ref-type="aff" rid="A45">45</xref></contrib><contrib contrib-type="author"><name><surname>Wolf</surname><given-names>Armin</given-names></name><xref ref-type="aff" rid="A46">46</xref></contrib><contrib contrib-type="author"><name><surname>Brandl</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A47">47</xref></contrib><contrib contrib-type="author"><name><surname>Rudolph</surname><given-names>Guenther</given-names></name><xref ref-type="aff" rid="A46">46</xref></contrib><contrib contrib-type="author"><name><surname>Olden</surname><given-names>Matthias</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Morrison</surname><given-names>Margaux A.</given-names></name><xref ref-type="aff" rid="A48">48</xref></contrib><contrib contrib-type="author"><name><surname>Morgan</surname><given-names>Denise J.</given-names></name><xref ref-type="aff" rid="A48">48</xref></contrib><contrib contrib-type="author"><name><surname>Schu</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="A49">49</xref><xref ref-type="aff" rid="A50">50</xref><xref ref-type="aff" rid="A51">51</xref><xref ref-type="aff" rid="A52">52</xref><xref ref-type="aff" rid="A53">53</xref></contrib><contrib contrib-type="author"><name><surname>Ahn</surname><given-names>Jeeyun</given-names></name><xref ref-type="aff" rid="A54">54</xref></contrib><contrib contrib-type="author"><name><surname>Silvestri</surname><given-names>Giuliana</given-names></name><xref ref-type="aff" rid="A55">55</xref></contrib><contrib contrib-type="author"><name><surname>Tsironi</surname><given-names>Evangelia E.</given-names></name><xref ref-type="aff" rid="A56">56</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Kyu Hyung</given-names></name><xref ref-type="aff" rid="A57">57</xref></contrib><contrib contrib-type="author"><name><surname>Farrer</surname><given-names>Lindsay A.</given-names></name><xref ref-type="aff" rid="A49">49</xref><xref ref-type="aff" rid="A50">50</xref><xref ref-type="aff" rid="A51">51</xref><xref ref-type="aff" rid="A52">52</xref><xref ref-type="aff" rid="A53">53</xref></contrib><contrib contrib-type="author"><name><surname>Orlin</surname><given-names>Anton</given-names></name><xref ref-type="aff" rid="A58">58</xref></contrib><contrib contrib-type="author"><name><surname>Brucker</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="A59">59</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Mingyao</given-names></name><xref ref-type="aff" rid="A60">60</xref></contrib><contrib contrib-type="author"><name><surname>Curcio</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="A61">61</xref></contrib><contrib contrib-type="author"><name><surname>Mohand-Saïd</surname><given-names>Saddek</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref><xref ref-type="aff" rid="A64">64</xref><xref ref-type="aff" rid="A65">65</xref></contrib><contrib contrib-type="author"><name><surname>Sahel</surname><given-names>José-Alain</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref><xref ref-type="aff" rid="A64">64</xref><xref ref-type="aff" rid="A65">65</xref><xref ref-type="aff" rid="A66">66</xref><xref ref-type="aff" rid="A67">67</xref></contrib><contrib contrib-type="author"><name><surname>Audo</surname><given-names>Isabelle</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref><xref ref-type="aff" rid="A64">64</xref><xref ref-type="aff" rid="A68">68</xref></contrib><contrib contrib-type="author"><name><surname>Benchaboune</surname><given-names>Mustapha</given-names></name><xref ref-type="aff" rid="A65">65</xref></contrib><contrib contrib-type="author"><name><surname>Cree</surname><given-names>Angela J.</given-names></name><xref ref-type="aff" rid="A69">69</xref></contrib><contrib contrib-type="author"><name><surname>Rennie</surname><given-names>Christina A.</given-names></name><xref ref-type="aff" rid="A70">70</xref></contrib><contrib contrib-type="author"><name><surname>Goverdhan</surname><given-names>Srinivas V.</given-names></name><xref ref-type="aff" rid="A69">69</xref></contrib><contrib contrib-type="author"><name><surname>Grunin</surname><given-names>Michelle</given-names></name><xref ref-type="aff" rid="A71">71</xref></contrib><contrib contrib-type="author"><name><surname>Hagbi-Levi</surname><given-names>Shira</given-names></name><xref ref-type="aff" rid="A71">71</xref></contrib><contrib contrib-type="author"><name><surname>Campochiaro</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Katsanis</surname><given-names>Nicholas</given-names></name><xref ref-type="aff" rid="A72">72</xref><xref ref-type="aff" rid="A73">73</xref><xref ref-type="aff" rid="A74">74</xref></contrib><contrib contrib-type="author"><name><surname>Holz</surname><given-names>Frank G.</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Blond</surname><given-names>Frédéric</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref><xref ref-type="aff" rid="A64">64</xref></contrib><contrib contrib-type="author"><name><surname>Blanché</surname><given-names>Hélène</given-names></name><xref ref-type="aff" rid="A75">75</xref></contrib><contrib contrib-type="author"><name><surname>Deleuze</surname><given-names>Jean-François</given-names></name><xref ref-type="aff" rid="A75">75</xref><xref ref-type="aff" rid="A76">76</xref></contrib><contrib contrib-type="author"><name><surname>Igo</surname><given-names>Robert P.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Truitt</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Peachey</surname><given-names>Neal S.</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A77">77</xref></contrib><contrib contrib-type="author"><name><surname>Meuer</surname><given-names>Stacy M.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Myers</surname><given-names>Chelsea E.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Moore</surname><given-names>Emily L.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Klein</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Hauser</surname><given-names>Michael A.</given-names></name><xref ref-type="aff" rid="A78">78</xref><xref ref-type="aff" rid="A79">79</xref><xref ref-type="aff" rid="A80">80</xref></contrib><contrib contrib-type="author"><name><surname>Postel</surname><given-names>Eric A.</given-names></name><xref ref-type="aff" rid="A78">78</xref></contrib><contrib contrib-type="author"><name><surname>Courtenay</surname><given-names>Monique D.</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Schwartz</surname><given-names>Stephen G.</given-names></name><xref ref-type="aff" rid="A81">81</xref></contrib><contrib contrib-type="author"><name><surname>Kovach</surname><given-names>Jaclyn L.</given-names></name><xref ref-type="aff" rid="A81">81</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>William K.</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Liew</surname><given-names>Gerald</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Tƒan</surname><given-names>Ava G.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Gopinath</surname><given-names>Bamini</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Merriam</surname><given-names>John C.</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>R. Theodore</given-names></name><xref ref-type="aff" rid="A24">24</xref><xref ref-type="aff" rid="A82">82</xref></contrib><contrib contrib-type="author"><name><surname>Khan</surname><given-names>Jane C.</given-names></name><xref ref-type="aff" rid="A41">41</xref><xref ref-type="aff" rid="A83">83</xref><xref ref-type="aff" rid="A84">84</xref></contrib><contrib contrib-type="author"><name><surname>Shahid</surname><given-names>Humma</given-names></name><xref ref-type="aff" rid="A84">84</xref><xref ref-type="aff" rid="A85">85</xref></contrib><contrib contrib-type="author"><name><surname>Moore</surname><given-names>Anthony T.</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A26">26</xref><xref ref-type="aff" rid="A86">86</xref></contrib><contrib contrib-type="author"><name><surname>McGrath</surname><given-names>J. Allie</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Laux</surname><given-names>Reneé</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Brantley</surname><given-names>Milam A.</given-names><suffix>Jr.</suffix></name><xref ref-type="aff" rid="A87">87</xref></contrib><contrib contrib-type="author"><name><surname>Agarwal</surname><given-names>Anita</given-names></name><xref ref-type="aff" rid="A87">87</xref></contrib><contrib contrib-type="author"><name><surname>Ersoy</surname><given-names>Lebriz</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Caramoy</surname><given-names>Albert</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Langmann</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Saksens</surname><given-names>Nicole T. M.</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>de Jong</surname><given-names>Eiko K.</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Hoyng</surname><given-names>Carel B.</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Cain</surname><given-names>Melinda S.</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Richardson</surname><given-names>Andrea J.</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Tammy M.</given-names></name><xref ref-type="aff" rid="A88">88</xref></contrib><contrib contrib-type="author"><name><surname>Blangero</surname><given-names>John</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Weeks</surname><given-names>Daniel E.</given-names></name><xref ref-type="aff" rid="A32">32</xref><xref ref-type="aff" rid="A89">89</xref></contrib><contrib contrib-type="author"><name><surname>Dhillon</surname><given-names>Bal</given-names></name><xref ref-type="aff" rid="A90">90</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M.</given-names></name><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Doheny</surname><given-names>Kimberly F.</given-names></name><xref ref-type="aff" rid="A91">91</xref></contrib><contrib contrib-type="author"><name><surname>Romm</surname><given-names>Jane</given-names></name><xref ref-type="aff" rid="A91">91</xref></contrib><contrib contrib-type="author"><name><surname>Klaver</surname><given-names>Caroline C. W.</given-names></name><xref ref-type="aff" rid="A34">34</xref><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Hayward</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Gorin</surname><given-names>Michael B.</given-names></name><xref ref-type="aff" rid="A92">92</xref><xref ref-type="aff" rid="A93">93</xref></contrib><contrib contrib-type="author"><name><surname>Klein</surname><given-names>Michael L.</given-names></name><xref ref-type="aff" rid="A88">88</xref></contrib><contrib contrib-type="author"><name><surname>Baird</surname><given-names>Paul N.</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>den Hollander</surname><given-names>Anneke I.</given-names></name><xref ref-type="aff" rid="A29">29</xref><xref ref-type="aff" rid="A94">94</xref></contrib><contrib contrib-type="author"><name><surname>Fauser</surname><given-names>Sascha</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Yates</surname><given-names>John R. W.</given-names></name><xref ref-type="aff" rid="A25">25</xref><xref ref-type="aff" rid="A26">26</xref><xref ref-type="aff" rid="A84">84</xref></contrib><contrib contrib-type="author"><name><surname>Allikmets</surname><given-names>Rando</given-names></name><xref ref-type="aff" rid="A24">24</xref><xref ref-type="aff" rid="A95">95</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jie Jin</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Schaumberg</surname><given-names>Debra A.</given-names></name><xref ref-type="aff" rid="A20">20</xref><xref ref-type="aff" rid="A96">96</xref><xref ref-type="aff" rid="A97">97</xref></contrib><contrib contrib-type="author"><name><surname>Klein</surname><given-names>Barbara E. K.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Hagstrom</surname><given-names>Stephanie A.</given-names></name><xref ref-type="aff" rid="A77">77</xref></contrib><contrib contrib-type="author"><name><surname>Chowers</surname><given-names>Itay</given-names></name><xref ref-type="aff" rid="A71">71</xref></contrib><contrib contrib-type="author"><name><surname>Lotery</surname><given-names>Andrew J.</given-names></name><xref ref-type="aff" rid="A69">69</xref></contrib><contrib contrib-type="author"><name><surname>Léveillard</surname><given-names>Thierry</given-names></name><xref ref-type="aff" rid="A62">62</xref><xref ref-type="aff" rid="A63">63</xref><xref ref-type="aff" rid="A64">64</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Kang</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A44">44</xref></contrib><contrib contrib-type="author"><name><surname>Brilliant</surname><given-names>Murray H.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Hewitt</surname><given-names>Alex W.</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A30">30</xref><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Swaroop</surname><given-names>Anand</given-names></name><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Chew</surname><given-names>Emily Y.</given-names></name><xref ref-type="aff" rid="A98">98</xref></contrib><contrib contrib-type="author"><name><surname>Pericak-Vance</surname><given-names>Margaret A.</given-names></name><xref ref-type="aff" rid="A22">22</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>DeAngelis</surname><given-names>Margaret</given-names></name><xref ref-type="aff" rid="A48">48</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>Stambolian</surname><given-names>Dwight</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>Haines</surname><given-names>Jonathan L.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A99">99</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>Iyengar</surname><given-names>Sudha K.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN3" ref-type="author-notes">‡</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Weber</surname><given-names>Bernhard H. F.</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>Abecasis</surname><given-names>Gonçalo R.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib><contrib contrib-type="author"><name><surname>Heid</surname><given-names>Iris M.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN3" ref-type="author-notes">‡</xref></contrib></contrib-group><aff id="A1"><label>1</label>Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA</aff><aff id="A2"><label>2</label>Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany</aff><aff id="A3"><label>3</label>Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA</aff><aff id="A4"><label>4</label>Institute of Human Genetics, University of Regensburg, Regensburg, Germany</aff><aff id="A5"><label>5</label>Kidney Epidemiology and Cost Center, Department of Internal Medicine - Nephrology, University of Michigan, Ann Arbor, MI 48109, USA</aff><aff id="A6"><label>6</label>School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia</aff><aff id="A7"><label>7</label>Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA</aff><aff id="A8"><label>8</label>Department of Ophthalmology, University of California San Diego and VA San Diego Health System, La Jolla, CA, USA</aff><aff id="A9"><label>9</label>Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology Harvard Medical School, Boston, MA, USA</aff><aff id="A10"><label>10</label>Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</aff><aff id="A11"><label>11</label>Department of Ophthalmology, Wilmer Eye Institute - Johns Hopkins University School of Medicine, Baltimore, MD, USA</aff><aff id="A12"><label>12</label>Department of Molecular Biology and Genetics - Johns Hopkins University School of Medicine, Baltimore, MD, USA</aff><aff id="A13"><label>13</label>Department of Neuroscience - Johns Hopkins University School of Medicine, Baltimore, MD, USA</aff><aff id="A14"><label>14</label>Institute of Genetic Medicine - Johns Hopkins University School of Medicine, Baltimore, MD, USA</aff><aff id="A15"><label>15</label>Institue de la Vision, Université Pierre et Marie Curie, Paris, France</aff><aff id="A16"><label>16</label>Hôpital Intercommunal de Créteil, Hôpital Henri Mondor - Université Paris Est Créteil, France</aff><aff id="A17"><label>17</label>University of Bonn - Department of Ophthalmology, Bonn, Germany</aff><aff id="A18"><label>18</label>Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA</aff><aff id="A19"><label>19</label>Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA</aff><aff id="A20"><label>20</label>Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA</aff><aff id="A21"><label>21</label>Department of Nutrition, Harvard School of Public Health, Boston, MA, USA</aff><aff id="A22"><label>22</label>John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA</aff><aff id="A23"><label>23</label>Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia</aff><aff id="A24"><label>24</label>Department of Ophthalmology Columbia University, New York, NY, USA</aff><aff id="A25"><label>25</label>UCL Institute of Ophthalmology, University College London, London, UK</aff><aff id="A26"><label>26</label>Moorfields Eye Hospital, London, UK</aff><aff id="A27"><label>27</label>Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA</aff><aff id="A28"><label>28</label>University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany</aff><aff id="A29"><label>29</label>Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands</aff><aff id="A30"><label>30</label>Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia</aff><aff id="A31"><label>31</label>South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA</aff><aff id="A32"><label>32</label>Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</aff><aff id="A33"><label>33</label>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK</aff><aff id="A34"><label>34</label>Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A35"><label>35</label>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands</aff><aff id="A36"><label>36</label>Quantitative Biomedical Research Center, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA</aff><aff id="A37"><label>37</label>Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA</aff><aff id="A38"><label>38</label>Neurobiology Neurodegeneration & Repair Laboratory (N-NRL), National Eye Institute, National Institutes of Health, Bethesda, MD, USA</aff><aff id="A39"><label>39</label>Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA</aff><aff id="A40"><label>40</label>Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia</aff><aff id="A41"><label>41</label>Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia</aff><aff id="A42"><label>42</label>Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China</aff><aff id="A43"><label>43</label>Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China</aff><aff id="A44"><label>44</label>Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China</aff><aff id="A45"><label>45</label>EyeCentre Southwest, Stuttgart, Baden-Württemberg, Germany</aff><aff id="A46"><label>46</label>University Eye Clinic, Ludwig-Maximilians-University, Munich, Germany</aff><aff id="A47"><label>47</label>Department of Ophthalmology, University Hospital Regensburg, Regensburg, Germany</aff><aff id="A48"><label>48</label>Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA</aff><aff id="A49"><label>49</label>Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA</aff><aff id="A50"><label>50</label>Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</aff><aff id="A51"><label>51</label>Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</aff><aff id="A52"><label>52</label>Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA</aff><aff id="A53"><label>53</label>Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA</aff><aff id="A54"><label>54</label>Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea</aff><aff id="A55"><label>55</label>Centre for Experimental Medicine, Queen's University, Belfast, UK</aff><aff id="A56"><label>56</label>Department of Ophthalmology, University of Thessaly, School of Medicine, Larissa, Greece</aff><aff id="A57"><label>57</label>Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea</aff><aff id="A58"><label>58</label>Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA</aff><aff id="A59"><label>59</label>Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</aff><aff id="A60"><label>60</label>Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</aff><aff id="A61"><label>61</label>Department of Ophthalmology, The University of Alabama at Birmingham, Birmingham, AL, USA</aff><aff id="A62"><label>62</label>INSERM, Paris, France</aff><aff id="A63"><label>63</label>Institut de la Vision, Department of Genetics, Paris, France</aff><aff id="A64"><label>64</label>CNRS, Paris, France</aff><aff id="A65"><label>65</label>Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, France</aff><aff id="A66"><label>66</label>Fondation Ophtalmologique Adolphe de Rothschild, Paris, France</aff><aff id="A67"><label>67</label>Académie des Sciences–Institut de France, Paris, France</aff><aff id="A68"><label>68</label>Department of Molecular Genetics, Institute of Ophthalmology, London, UK</aff><aff id="A69"><label>69</label>Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK</aff><aff id="A70"><label>70</label>University Hospital Southampton, Southampton, UK</aff><aff id="A71"><label>71</label>Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel</aff><aff id="A72"><label>72</label>Center for Human Disease Modeling, Duke University, Durham, NC, USA</aff><aff id="A73"><label>73</label>Department of Cell Biology, Duke University, Durham, NC, USA</aff><aff id="A74"><label>74</label>Department of Pediatrics, Duke University, Durham, NC, USA</aff><aff id="A75"><label>75</label>CEPH Fondation Jean Dausset Paris, France</aff><aff id="A76"><label>76</label>CEA – IG – Centre National de Génotypage Evry Cédex, France</aff><aff id="A77"><label>77</label>Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA</aff><aff id="A78"><label>78</label>Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA</aff><aff id="A79"><label>79</label>Department of Medicine, Duke University Medical Center, Durham, NC, USA</aff><aff id="A80"><label>80</label>Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA</aff><aff id="A81"><label>81</label>Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, FL, USA</aff><aff id="A82"><label>82</label>Department of Ophthalmology, NYU School of Medicine, New York, NY, USA</aff><aff id="A83"><label>83</label>Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia</aff><aff id="A84"><label>84</label>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</aff><aff id="A85"><label>85</label>Department of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK</aff><aff id="A86"><label>86</label>Department of Ophthalmology UCSF Medical School, San Francisco, CA USA</aff><aff id="A87"><label>87</label>Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, TN, USA</aff><aff id="A88"><label>88</label>Casey Eye Institute, Oregon Health & Science University, Portland OR, USA</aff><aff id="A89"><label>89</label>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA</aff><aff id="A90"><label>90</label>School of Clinical Sciences University of Edinburgh, Scotland, UK</aff><aff id="A91"><label>91</label>Center for Inherited Disease Research (CIDR) Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore, MD, USA</aff><aff id="A92"><label>92</label>Department of Ophthalmology, David Geffen School of Medicine—UCLA, Stein Eye Institute, Los Angeles, CA, USA</aff><aff id="A93"><label>93</label>Department of Human Genetics, David Geffen School of Medicine—UCLA, Los Angeles, CA, USA</aff><aff id="A94"><label>94</label>Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands</aff><aff id="A95"><label>95</label>Department of Pathology & Cell Biology, Columbia University, New York, NY, USA</aff><aff id="A96"><label>96</label>Center for Translational Medicine, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA</aff><aff id="A97"><label>97</label>Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA</aff><aff id="A98"><label>98</label>Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA</aff><aff id="A99"><label>99</label>Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA</aff><author-notes><corresp id="FN1"><label>*</label>Correspondence to: <email>iris.heid@klinik.uni-regensburg.de</email> (I.M.H.), <email>goncalo@umich.edu</email> (G.R.A.), <email>ski@case.edu</email> (S.K.I.)</corresp><fn id="FN2"><label>†</label><p>These authors contributed equally to this work</p></fn><fn id="FN3"><label>‡</label><p>These authors jointly supervised this work</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>17</day><month>1</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>21</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>21</day><month>6</month><year>2016</year></pub-date><volume>48</volume><issue>2</issue><fpage>134</fpage><lpage>143</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.3448</pmc-comment>
<permissions><license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms"><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10<sup>–8</sup>) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near <italic>MMP9</italic> (difference-P = 4.1×10<sup>–10</sup>). Very rare coding variants (frequency < 0.1%) in <italic>CFH</italic>, <italic>CFI</italic>, and <italic>TIMP3</italic> suggest causal roles for these genes, as does a splice variant in <italic>SLC16A8</italic>. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.</p></abstract></article-meta></front><body><p id="P2">Advanced age-related macular degeneration (AMD) is a neurodegenerative disease and the leading cause of vision loss among the elderly affecting 5% of those >75 years of age<sup><xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref></sup>. The disease is characterized by reduced retinal pigment epithelium (RPE) function and photoreceptor loss in the macula. Advanced AMD is classified as wet (choroidal neovascularization, CNV, when accompanied by angiogenesis) or dry AMD (geographic atrophy, GA, when angiogenesis is absent). These advanced stages of disease are typically preceded by clinically asymptomatic earlier stages<sup><xref rid="R3" ref-type="bibr">3</xref></sup>. Advanced AMD is estimated to affect 10 million patients worldwide, reaching >150 million for earlier stages<sup><xref rid="R4" ref-type="bibr">4</xref></sup>. At present, understanding of disease biology and therapies remains limited<sup><xref rid="R5" ref-type="bibr">5</xref></sup>.</p><p id="P3">Genetic variants can help uncover disease mechanisms and provide entry points into therapy. Analyses of common variation have uncovered numerous risk loci for many complex diseases (see Web Resources) including 21 loci for AMD<sup><xref rid="R6" ref-type="bibr">6</xref>-<xref rid="R12" ref-type="bibr">12</xref></sup>. However translation into biological insights remains a challenge, since the functional consequences of disease-associated common variants are typically subtle<sup><xref rid="R13" ref-type="bibr">13</xref></sup> and hard to decipher.</p><p id="P4">With advances in sequencing technology, genetic analyses are gradually extending to rare variants, which often have more obvious functional consequences<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R15" ref-type="bibr">15</xref></sup> and can thus accelerate translation into biological understanding<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R16" ref-type="bibr">16</xref></sup>. For example, identifying multiple disease-associated coding variants (particularly knock-out alleles) in the same gene provides strong evidence that disrupting gene function leads to disease<sup><xref rid="R17" ref-type="bibr">17</xref></sup>. So far, studies that implicate specific rare variants in complex diseases either rely on special populations<sup><xref rid="R8" ref-type="bibr">8</xref>,<xref rid="R18" ref-type="bibr">18</xref>,<xref rid="R19" ref-type="bibr">19</xref></sup>, on targeted examinations of a few genes<sup><xref rid="R7" ref-type="bibr">7</xref>,<xref rid="R9" ref-type="bibr">9</xref>-<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R20" ref-type="bibr">20</xref>,<xref rid="R21" ref-type="bibr">21</xref></sup>, or on genome-wide assessments of relatively modest numbers of individuals<sup><xref rid="R22" ref-type="bibr">22</xref>-<xref rid="R25" ref-type="bibr">25</xref></sup>. In contrast, systematic analyses of common variation are now available in hundreds of thousands of phenotyped individuals<sup><xref rid="R26" ref-type="bibr">26</xref>,<xref rid="R27" ref-type="bibr">27</xref></sup>. Thus, there remains considerable uncertainty about the relative role of rare variants in complex disease and about the sample sizes and study designs that will enable systematic identification of these variants<sup><xref rid="R16" ref-type="bibr">16</xref></sup>.</p><p id="P5">Here, we set out to systematically examine common and rare variation of AMD in the International AMD Genomics Consortium (IAMDGC). The preceding largest study of AMD examined ∼2.4 million variants including ∼18,000 imputed or genotyped protein-altering variants using meta-analysis<sup><xref rid="R6" ref-type="bibr">6</xref></sup>. Customizing a chip for <italic>de novo</italic> centralized genotyping, we analyze >12 million variants including 163,714 directly typed protein-altering variants in 43,566 unrelated subjects of predominantly European ancestry. Our study constitutes a detailed simultaneous assessment of common and rare variation in a complex disease and a large sample, setting expectations for other well-powered studies.</p><sec sec-type="results" id="S1"><title>Results</title><sec id="S2" sec-type="methods"><title>The study data and genomic heritability</title><p id="P6">We gathered advanced AMD cases with GA and/or CNV, intermediate AMD cases, and control subjects across 26 studies (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 1</xref>). While recruitment and ascertainment strategies varied (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>), DNA samples were collected and genotyped centrally. Making maximal use of genotyping technologies, we utilized a chip with (i) the usual genome-wide variant content, (ii) exome content comparable to the exome chip (adding protein-altering variants from across all exons), and a specific customization to add (iii) protein-altering variants detected by our prior sequencing of known AMD loci (see <bold>Methods</bold>) and (iv) previously observed and predicted variation in <italic>TIMP3</italic> and <italic>ABCA4</italic>, two genes implicated in monogenic retinal dystrophies. After quality control, we retained 439,350 directly typed variants including a grid of 264,655 primarily non-coding (93%) common variants (frequency among controls >1%) and 163,714 protein-altering variants (including 8,290 from known AMD loci), mostly rare (88% with frequency among controls ≤1%). Imputation to the 1000 Genomes reference panel enabled examining a total of 12,023,830 variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3A</xref>). Our final data set included a total of 43,566 subjects consisting of 16,144 advanced AMD patients and 17,832 control subjects of European ancestry for our primary analysis, as well as 6,657 Europeans with intermediate disease and 2,933 subjects with Non-European ancestry (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3B</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Figure 1</xref>).</p><p id="P7">Altogether, our genotyped markers accounted for 46.7%<sup><xref rid="R28" ref-type="bibr">28</xref></sup> of variability in advanced AMD risk in the European ancestry subjects (95% confidence interval [CI] 44.5% to 48.8%). Regarding AMD subtypes, estimates for CNV (h<sup><xref rid="R2" ref-type="bibr">2</xref></sup> = 44.3%, CI 42.2% to 46.5%) and GA (h<sup><xref rid="R2" ref-type="bibr">2</xref></sup> = 52.3%, CI 47.2% to 57.4%) were similar; bivariate analyses<sup><xref rid="R29" ref-type="bibr">29</xref></sup> showed genetic correlation of 0.85 (CI 0.78 to 0.92) between disease subtypes.</p></sec><sec id="S3"><title>Thirty-Four Susceptibility Loci for AMD</title><p id="P8">We first conducted a genome-wide single variant analysis of the >12 million genotyped or imputed variants (applying genomic control λ=1.13) comparing the 16,144 advanced AMD patients and 17,832 controls of European ancestry (full results online; see <bold>Web resources</bold>). We obtained >7000 genome-wide significant variants (P ≤ 5×10<sup>–8</sup>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Figure 2</xref>). Sequential forward selection (<xref rid="SD1" ref-type="supplementary-material">Supplementary Figure 3</xref>) identified 52 independently associated variants at P ≤ 5×10<sup>–8</sup> (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 1</xref>). These are distributed across 34 locus regions (<xref rid="F1" ref-type="fig">Figure 1A</xref>), each extending across the identified and correlated variants, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup>≥0.5, ±500kb (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>). The 34 loci include 16 loci that reached genome-wide significance for the first time (novel loci, <xref rid="T1" ref-type="table">Table 1</xref>) and include genes with compelling biology like extra-cellular matrix genes (<italic>COL4A3</italic>, <italic>MMP19</italic>, <italic>MMP9)</italic>, an ABC transporter linked to HDL cholesterol (<italic>ABCA1)</italic>, and a key activator in immune function (<italic>PILRB)</italic>. Also included are 18 of the 21 AMD loci that reached genome-wide significance previously<sup><xref rid="R6" ref-type="bibr">6</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup> (known loci, <xref rid="T1" ref-type="table">Table 1</xref>), between-study heterogeneity was low, particularly for the new loci (<xref rid="SD1" ref-type="supplementary-material">Supplementary Note 1</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 6, 7</xref>).</p><p id="P9">Most associated variants are common (45 out of 52) with fully conditioned odds ratios (OR) from 1.1 to 2.9 (<xref rid="F1" ref-type="fig">Figure 1B</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>) with two interacting variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary Note 2</xref>). We also observed seven rare variants with frequencies between 0.01% and 1% and ORs between 1.5 and 47.6 (<xref rid="F1" ref-type="fig">Figure 1B</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). All of these variants were also rare in Non-European ancestries (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 8</xref>, extended association results on Non-European in <xref rid="SD1" ref-type="supplementary-material">Supplementary File 2</xref>). All seven rare variants are located in/near complement genes: four previously described non-synonymous (<italic>CFH</italic>:Arg1210Cys, <italic>CFI</italic>:Gly119Arg, <italic>C9</italic>:Pro167Ser, <italic>C3</italic>:Lys155Gln)<sup><xref rid="R7" ref-type="bibr">7</xref>-<xref rid="R11" ref-type="bibr">11</xref></sup>; three others (CFH: rs148553336, rs191281603, rs35292876) described here for the first time including two with the rare allele decreasing the disease risk. . To ensure validity of our results, we verified associations of lead variants in sensitivity analyses that relied on alternate association tests, adjusted for age, gender, or ten ancestry principal components, or were restricted to population-based controls or controls ≥ 50 years of age (data not shown). Altogether, our genome-wide single variant analysis nearly doubles the number of AMD loci and variants.</p></sec><sec id="S4"><title>Prioritizing variants within 52 association signals</title><p id="P10">It is often challenging to translate common variant association signals into mechanistic understanding of biology; two key challenges are (i) variants with similar signals because of linkage disequilibrium and (ii) subtle functional consequences. Without narrowing lists of candidate variants, follow-up functional experiments are complicated. To prioritize among nearby variants, we computed each variant's ability to explain the observed signal and derived, for each of the 52 signals, the smallest set of variants that included the causal variant with 95% probability <sup><xref rid="R30" ref-type="bibr">30</xref>,<xref rid="R31" ref-type="bibr">31</xref></sup>. The 52 credible sets each included from 1 to >100 variants (total of 1,345 variants, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 3</xref>). Twenty-seven (of 52) sets were small with ≤10 variants (19 with ≤5 variants, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 9</xref>); seven sets included only one variant. Among the 205 variants with >5% probability of being causal, we observe 11 protein-altering (all non-synonymous) variants (versus 2 expected assuming 1% protein-altering variants, P for enrichment = 8.7×10<sup>–6</sup>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 10</xref>). We recognize that the analysis has limitations [for example, when causal variants when the signal is due to a combination of multiple variants, as in the counter example in <xref rid="SD1" ref-type="supplementary-material">Supplementary Figure 4</xref>].</p></sec><sec id="S5"><title>Rare Variant Association Signals</title><p id="P11">Analysis of rare variants that alter peptide sequences (non-synonymous), truncate proteins (premature stop), or affect RNA splicing (splice site) can help to identify causal mechanisms – particularly when multiple associated variants reside in the same gene<sup><xref rid="R16" ref-type="bibr">16</xref>,<xref rid="R32" ref-type="bibr">32</xref></sup>. We examined the cumulative effect of rare protein-altering variants in each ancestry group. Genome-wide, no signal was detected with P ≤ 0.05/17,044 = 2.9×10<sup>–6</sup> outside the 34 AMD loci (<xref rid="F1" ref-type="fig">Figure 1C</xref>). Within the 34 loci, we found 14 genes with significant disease burden (P < 0.05/703 genes = 7.1×10<sup>–5</sup>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 11</xref>). To eliminate settings where a rare variant burden finding is a linkage disequilibrium shadow of a nearby common variant, we re-evaluated each burden signal conditioning on nearby single variants (from <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). Four of the 14 genes retained P < 0.05/703 = 7.1×10<sup>–5</sup> in this analysis (<italic>CFH</italic>, <italic>CFI</italic>, <italic>TIMP3</italic>, <italic>SLC16A8</italic>; conditioned P = 1.2×10<sup>–6</sup>, 1.0×10<sup>–8</sup>, 9.0×10<sup>–8</sup>, or 3.1×10<sup>–6</sup>, respectively, <xref rid="T2" ref-type="table">Table 2</xref>). Sensitivity analyses provide similar (excluding previously sequenced subjects) and extended results (prioritizing variants with high predicted functionality, <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 3</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 12</xref>).</p><p id="P12">Several interesting patterns emerge, many of which we owe to our chip design. First, three of the four rare variant burden signals (<italic>CFH</italic>, <italic>CFI</italic>, <italic>TIMP3</italic>) are due to variants with frequency <0.1%, all genotyped (<xref rid="SD1" ref-type="supplementary-material">Supplementary File 4</xref>). Many human genetic studies have used frequency thresholds of 1% to 5% as a working definition of “rare”, but our data suggests that trait associated variants with clear function may often be much rarer – necessitating very large sample sizes for analysis. In two genes (<italic>CFH, CFI</italic>), the rare burden was detected because we enriched arrays with variants from previous sequencing of AMD loci<sup><xref rid="R10" ref-type="bibr">10</xref></sup> (54 of 80 variants). The burden findings in <italic>CFH</italic> (new, <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 4</xref>) and <italic>CFI</italic><sup><xref rid="R9" ref-type="bibr">9</xref></sup> together with variants <italic>CFH:</italic>Arg1210Cys and <italic>CFI</italic>:Gly119Arg<sup><xref rid="R7" ref-type="bibr">7</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup>, corroborate a causal role for these genes in AMD etiology.</p><p id="P13">The third signal (<italic>TIMP3</italic>) was in a gene previously associated with Sorsby's fundus dystrophy, a rare monogenic disease with early onset at <45 years of age but with clinical presentation strikingly similar to AMD<sup><xref rid="R33" ref-type="bibr">33</xref>,<xref rid="R34" ref-type="bibr">34</xref></sup>. Because the majority of Sorsby's alleles disrupt cysteine-cysteine bonds in <italic>TIMP3</italic>, we arrayed all possible cysteine disrupting sites together with other previously described Sorsby's risk alleles <sup><xref rid="R33" ref-type="bibr">33</xref>,<xref rid="R34" ref-type="bibr">34</xref></sup>. The nine rarest <italic>TIMP3</italic> variants were cumulatively associated with >30-fold increased risk of disease. <italic>TIMP3</italic> resides in an established AMD locus<sup><xref rid="R5" ref-type="bibr">5</xref>,<xref rid="R35" ref-type="bibr">35</xref></sup> targeted in previous sequencing efforts<sup><xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R35" ref-type="bibr">35</xref></sup> that were too small to evaluate rare variation on this scale (1 variant in 17,832 controls versus 29 variants in 16,144 cases). Interestingly, although Sorsby-associated <italic>TIMP3</italic> variants typically occur in exon 5, four of the unpaired cysteine residues we observed map to other exons – perhaps because unpaired cysteines in different locations impair protein folding in different ways. AMD cases with these rare <italic>TIMP3</italic> risk alleles still exhibited higher counts of AMD risk alleles across the genome than controls, suggesting that <italic>TIMP3</italic> is not a monogenic cause of AMD but contributes to disease together with alleles at the other risk loci. Our finding illustrates a locus where complex and monogenic disorders arise from variation in the same gene, similar to <italic>MC4R</italic> and <italic>POMC</italic> in obesity<sup><xref rid="R36" ref-type="bibr">36</xref></sup> or <italic>UMOD</italic> in kidney function<sup><xref rid="R37" ref-type="bibr">37</xref></sup>. In a similar approach, we analyzed 146 rare protein-altering variants in <italic>ABCA4</italic>, a gene underlying Stargardt disease<sup><xref rid="R38" ref-type="bibr">38</xref></sup>, but found no association (P=0.97).</p><p id="P14">The rare variant burden signal in <italic>SLC16A8</italic> was primarily driven by a putative splice variant (c.214+1G>C, rs77968014, minor allele frequency among controls, CAF = 0.81%, OR = 1.5, imputed with R<sup><xref rid="R2" ref-type="bibr">2</xref></sup>=0.87, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 4</xref>). This is not a burden from multiple rare variants, but a single variant emerging as significant due to the reduced multiple testing from gene-wide testing (single variant association P = 9.1×10<sup>-6</sup>, conditioned on rs8135665 P = 1.3×10<sup>-6</sup>). This variant is interesting as it is predicted to disrupt processing of the encoded transcript (as +1 G variant, Human Splicing Finder 3.0). S<italic>LC16A8</italic> encodes a cell membrane transporter, involved in transport of pyruvate, lactate and related compounds across cell membranes<sup><xref rid="R39" ref-type="bibr">39</xref></sup>. This class of proteins mediates the acidity level in the outer retinal segments, and <italic>SLC16A8</italic> gene knock-out animals have changes in visual function and scotopic electroretinograms, but not overt retinal pathology<sup><xref rid="R40" ref-type="bibr">40</xref></sup>. Interestingly, a progressive loss of <italic>SLC16A8</italic> expression in eyes affected with GA was reported with increasing severity of disease<sup><xref rid="R41" ref-type="bibr">41</xref></sup>. In summary, our chip design and our large data set enabled us not only to detect interesting features of AMD genetics, but also to provide guidance for future investigations on rare variants.</p></sec><sec id="S6"><title>From Disease Loci to Biological Insights</title><p id="P15">Many analyses can further narrow the list of candidate genes in our loci. We annotated the 368 genes closest to our 52 association signals (index variant and proxies, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> ≥0.5, ±100kb, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 5</xref>), noting among these the genes those that contained associated credible set variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary File 3</xref>) or a rare variant burden (<xref rid="T2" ref-type="table">Table 2</xref>) – these are the highest priority candidates, consistent with previous analysis of putative cis-regulatory variants<sup><xref rid="R42" ref-type="bibr">42</xref></sup>. We further checked whether genes were expressed in retina (82.6% of genes) or RPE/choroid (86.4%, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 6</xref>). We sought relevant eye phenotypes in genetically modified mice (observed in 32 of the 368 queried genes, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 7</xref>). We tagged genes in biological pathways enriched across loci, such as the alternative complement pathway, HDL transport, and extracellular matrix organization and assembly (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 13</xref>) – highlighting genes that connect multiple pathways (<italic>COL4A3</italic>/<italic>COL4A4</italic>, <italic>ABCA1</italic>, <italic>MMP9</italic>, and <italic>VTN</italic>). We also highlighted genes that were approved or experimental drug targets (31 of the 368 queried, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 8</xref>). Finally, we prioritized genes where at least one of the credible set variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary File 3</xref>) was protein-altering or located in a putative functional region (promoter, 3′/5′ UTR).</p><p id="P16">All this information is summarized in the gene priority score table (<xref rid="SD1" ref-type="supplementary-material">Supplementary File 9</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 5</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 14</xref>), which uses a simple customizable scoring scheme to assign priority: the scheme using equal weights for each column assigns highest scores (<xref rid="F2" ref-type="fig">Figure 2A</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 15</xref>) to genes such as master regulators of immune function (<italic>PILRB)</italic>, matrix metalloproteinase genes (<italic>MMP9, MMP19)</italic>, genes involved in in lipid metabolism (<italic>ABCA1, GPX4)</italic>, an inhibitor of the complement cascade (<italic>VTN</italic>), another collagen gene (<italic>COL4A3</italic>), a gene causing a developmental monogenic disorder (<italic>PTPN11</italic>), and a retinol dehydrogenase (<italic>RDH5)</italic>. Six of these are current drug targets (<italic>ABCA1</italic>, <italic>MMP19</italic>, <italic>RDH5, PTPN11, VTN, GPX4</italic>). In the known AMD loci, the highest scores per locus included the usual suspects (<italic>CFH</italic>, <italic>CFI</italic>, <italic>CFB</italic>, <italic>C3</italic>, and <italic>APOE</italic>) as well as <italic>TIMP3</italic> and <italic>SLC16A8</italic> (<xref rid="F2" ref-type="fig">Figure 2B</xref>). This summary of evidence is not amenable to formal statistical enrichment testing, but may help prioritize genes for follow-up functional experiments.</p></sec><sec id="S7"><title>Commonalities and differences of advanced AMD subtypes</title><p id="P17">Previously identified risk variants all contribute to the two advanced AMD subtypes, CNV and GA. We compared association signals between our 10,749 cases with CNV and 3,235 cases with GA. Four of the 34 lead variants show significant difference (P<sub>diff</sub> < 0.05/34 = 0.00147) between disease subtypes (in the loci <italic>ARMS2/HTRA1</italic>, <italic>CETP</italic>, <italic>MMP9</italic>, <italic>SYN3/TIMP3,</italic><xref rid="F3" ref-type="fig">Figure 3A</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 16</xref>). Variant rs42450006 upstream of <italic>MMP9</italic> was the only one that was specific to one subtype, being exclusively associated with CNV (frequency in controls = 14.1%; OR<sub>CNV</sub> = 0.78 vs. OR<sub>GA</sub> = 1.04; P<sub>diff</sub> = 4.1×10<sup>–10</sup>), but not with GA (P<sub>GA</sub>=0.39, Supplementary Note 6). The <italic>MMP9</italic> signal for neovascular disease fits well with prior evidence: upregulation of <italic>MMP9</italic> appears to induce neovascularization<sup><xref rid="R43" ref-type="bibr">43</xref></sup> and interacts with <italic>VEGF</italic> signaling in the RPE<sup><xref rid="R44" ref-type="bibr">44</xref></sup>. VEGF currently provides an effective therapy for patients with CNV, but the struggle to keep vision continues. Beyond confirming a shared genetic predisposition of the two subtypes, our data identifies – for the first time – one variant that is specific to one subtype.</p></sec><sec id="S8"><title>Commonalities and differences of advanced and early AMD</title><p id="P18">We evaluated our association signals in 6,657 individuals with intermediate AMD, defined as having more than five macular drusen greater than 63μm and/or pigmentary changes in the RPE. Examining all genotyped variants<sup><xref rid="R28" ref-type="bibr">28</xref></sup>, we found a correlation of 0.78, indicating substantial overlap between genetic determinants of advanced and intermediate AMD (95% CI 0.69 to 0.87). Among our 34 index variants, 24 showed nominally significant association (P<sub>intermediate</sub> ≤ 0.05) with intermediate AMD (2 expected, P<sub>binomial</sub> = 4.8×10<sup>–24</sup>); all had ORs in the same direction but smaller in magnitude (<xref rid="F3" ref-type="fig">Figure 3B</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 17</xref>). The other 10 variants showed no association with intermediate AMD (P<sub>intermediate</sub> > 0.05), despite sufficient power (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 18</xref>). Interestingly, these 10 variants point to 7 extra-cellular matrix genes (<italic>COL15A1</italic>, <italic>COL8A1</italic>, <italic>MMP9</italic>, <italic>PCOLCE</italic>, <italic>MMP19</italic>, <italic>CTRB1</italic>/2, <italic>ITGA7,</italic><xref rid="SD1" ref-type="supplementary-material">Supplementary Table 19</xref>), based on which one may hypothesize that the extra-cellular matrix points to a disease subtype without early stage manifestation or with extremely rapid progression. If confirmed, a group of rapidly progressing patients or without early symptoms might eventually derive maximum benefit from genetic diagnosis and future preventive therapies.</p></sec><sec id="S9"><title>An Accounting of AMD Genetics</title><p id="P19">To account for progress made here in understanding AMD genetics, we estimated the proportion of disease risk explained by our 52 independent variants and compared it to our initial estimates of heritability obtained by examining all genotyped variants. We computed a weighted risk score of the 52 variants<sup><xref rid="R45" ref-type="bibr">45</xref></sup> and modeled a population risk score distribution (see <bold>Materials and Methods</bold>). Individuals in the highest decile of genetic risk have a 44-fold increased risk of developing advanced AMD compared to the lowest decile; of these, 22.7% are predicted to have AMD in an elderly general population above 75 years of age with ∼5% disease prevalence (<xref rid="F4" ref-type="fig">Figure 4A</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 20</xref>). Altogether, the 52 variants explain 27.2% of disease variability (<xref rid="F4" ref-type="fig">Figure 4B</xref>, also highlighting results based on other prevalence assumptions), including a 1.4% contribution from rare variants. The 52 identified variants thus explain more than half of the genomic heritability; the balance might be attributed to additional variation not studied here, or to genetic interaction with environmental factors such as smoking, diet or sunlight exposure.</p></sec></sec><sec sec-type="discussion" id="S10"><title>Discussion</title><p id="P20">We set out to improve our understanding of rare and common genetic variation for macular degeneration biology, to guide the development of therapeutic interventions and facilitate early diagnosis, monitoring and prevention of disease. We systematically examine rare variation (through direct genotyping) and common variation (through genotyping and imputation) for AMD in a study designed to discover >80% of associated protein-altering variants with an allele frequency of >0.1% and >3-fold increased disease risk (or >0.5% frequency and >1.8-fold increased disease risk). Our study provides a simultaneous assessment of common and rare variation enabling us to understand the relative roles of rare and common variants and the scientific insights to be gained from rare variation.</p><p id="P21">Rare protein-altering variants are an attractive target for genetic studies because most of these variants are expected to damage gene function. Furthermore, observing that many rare variants in a gene are, together, associated with a change in disease risk strongly suggests that the gene is causally implicated in disease biology and – further – suggests the consequences of mimicking or blocking gene action using a drug. Our study demonstrates that when rare variants are systematically assessed genome-wide, significant signals can be assigned to single rare variants as well as to rare variant burden in individual genes.</p><p id="P22">Our study also demonstrates the challenges of these analyses. For three of the genes where we identified a rare variant burden, the accumulated evidence was spread across very rare variants with frequencies <0.1% in controls. Most of these variants derived from sequencing AMD patients. This emphasizes the value of a hybrid approach with direct targeted sequencing of patient samples for variant discovery, followed by genotyping in larger samples for association analysis. Another conclusion is about required sample sizes: although such rare variants are expected to exist in nearly all genes, no rare variant burden was observed in most of the 34 loci we studied. For these loci, identifying causal mechanisms through the study of rare protein-altering variants will require a combination of more sequencing and even larger sample sizes. While our findings of rare variant burden are predominantly from targeted enrichment, the knowledge about effect sizes and frequencies of contributing variants illustrates that applying the approach genome-wide to detect new loci requires extremely large sample sizes. In our view, a recent estimate that sequencing of 25,000 patients will be needed to identify genes where rare variants have a substantial impact on disease risk is likely to be optimistic, particularly given the fact that effect sizes for AMD risk alleles appear to be larger than for many other complex traits <sup><xref rid="R16" ref-type="bibr">16</xref></sup>.</p><p id="P23">In addition to corroborating previous reports of rare variants that disrupt genes in the complement pathway and lead to large increases in disease risk, our study also includes two unexpected rare variant findings. First, we show that a putative splice variant in <italic>SLC16A8</italic> can greatly increase the risk of age-related macular degeneration – providing strong evidence that the gene is directly involved in disease biology. <italic>SLC16A8</italic> is a lactate transporter expressed<sup><xref rid="R39" ref-type="bibr">39</xref></sup> specifically by the RPE; a deficit of lactate transport results in acidification of the retina and photoreceptor dysfunction in <italic>Slc16a8</italic> knock-out mice<sup><xref rid="R40" ref-type="bibr">40</xref></sup>. Second, we show a >30-fold excess of rare <italic>TIMP3</italic> mutations among putative cases of macular degeneration. <italic>TIMP3</italic> is an especially attractive candidate that has been the subject of previous, underpowered, genetic association studies.</p><p id="P24">While it has been hypothesized that studies of rare and low frequency genetic variants will greatly increase the proportion of genetic risk that can be explained, our results don't support this. Our study and others successfully identify many low frequency disease risk alleles, and these provide clues about disease biology, but our results also show that common variants make a much larger contribution to disease risk. Common variants also suggest interesting leads and pathways for future analysis (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 15</xref>, <xref rid="F2" ref-type="fig">Figure 2A</xref>), including attractive candidates such as immune regulators (<italic>PILRB)</italic>, genes implicated in mouse ocular phenotypes (<italic>MMP9, MMP19, COL4A3, PTPN11, GPX4,</italic> and <italic>RDH5)</italic>, and proven drug targets (<italic>ABCA1</italic>, MMP19, <italic>RDH5, PTPN11, VTN, GPX4</italic>). In a literature search, we identified no previous candidate gene association studies targeting our novel loci, although several model organism, cellular, and functional studies evaluated potential links between genes in these loci and AMD (highlights of this search in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 15</xref>) and a few loci were nominally associated and proposed as candidates in prior genome-wide searches <sup><xref rid="R46" ref-type="bibr">46</xref>,<xref rid="R47" ref-type="bibr">47</xref></sup>. As richer functional annotations of the genome<sup><xref rid="R48" ref-type="bibr">48</xref></sup> become available in diverse cell types, systematic assessment of overlap between these and our loci should clarify disease biology.</p><p id="P25">Our study also suggests additional important observations. While our results show that the majority of genetic risk is shared between GA and CNV, we also identify – for the first time – a variant that is specific to one advanced AMD subtype: a genetic variant near <italic>MMP9</italic> is specific to CNV, a candidate gene also supported by prior gene expression analyses in the Bruch's membrane of patients with neovascular disease<sup><xref rid="R49" ref-type="bibr">49</xref></sup>. Future efforts extending to longitudinal data might help improve the dissection of pure CNV and pure GA and their genetic make-up even further. If substantiated, the fact that nearly all disease associated variants modulate risk of both CNV and GA has potentially significant therapeutic consequences. It implies that individuals at high risk of CNV are also at high risk of GA. This suggests that therapeutic strategies which mitigate CNV but not GA will only provide temporary relief to patients – who are likely to remain at high risk of developing GA and may still require future interventions to prevent it.</p><p id="P26">Therefore, our findings have several important implications for future studies of rare variation in human complex traits. First, they clearly emphasize the need for very large sample sizes in population studies: the functionally most interesting variants we identify have frequencies in the range of 0.01 – 1.0% and, despite their strong impact on disease risk, could only be implicated using 10,000s of individuals. Second, they illustrate the value of hybrid approaches, where sequencing is used to detect interesting variants and custom arrays and imputation are used to examine these variants in very large samples. Since all the large effect rare variants we identify reside in or near GWAS loci, as with most complex trait associated rare variants <sup><xref rid="R7" ref-type="bibr">7</xref>-<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R20" ref-type="bibr">20</xref>,<xref rid="R21" ref-type="bibr">21</xref>,<xref rid="R23" ref-type="bibr">23</xref>,<xref rid="R50" ref-type="bibr">50</xref></sup>, focused studies around GWAS loci may continue to be a cost-effective compromise. Third, our analysis of cysteine variants in <italic>TIMP3</italic> illustrates not only the potential for targeted variant discovery but the critical need to understand the consequences of rare variants when analyzing them together. While very large samples will be needed, our results also show that the effort to extend genetic studies to rare variants is worthwhile as these variants can pinpoint causal genes and advance our understanding of disease biology.</p></sec><sec id="S11"><title>Online Methods</title><sec id="S12"><title>Study data and phenotype</title><p id="P27">In the International AMD Genomics Consortium (IAMDGC), we gathered 26 studies with each including (i) advanced AMD cases with GA and/or CNV in at least one eye and age at first diagnosis ≥ 50 years, (ii) intermediate AMD cases with pigmentary changes in the RPE or more than five macular drusen greater than 63μm and age at first diagnosis ≥ 50 years, or (iii) controls without known advanced or intermediate AMD. Recruitment and ascertainment strategies varied by study (<xref rid="SD1" ref-type="supplementary-material">Supplementary Tables 1</xref> and <xref rid="T2" ref-type="table">2</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 7</xref>). All groups collected data according to the Declaration of Helsinki principles. Study participants provided informed consent and protocols were reviewed and approved by local ethics committees.</p></sec><sec id="S13"><title>DNA and chip design</title><p id="P28">We gathered DNA samples of more than 50,000 individuals. Groups with very limited amounts of available DNA contributed aliquots after whole-genome amplification (8% of subjects).</p><p id="P29">We utilized a custom-modified HumanCoreExome array by Illumina, Inc., which includes (i) tagging variants across the genome (genome chip content) and (ii) a catalogue of protein-altering variants (exome chip content). Our customization of the array included three additional tiers to enrich for variants from 22 AMD loci implicated by our previous genome-wide association analysis<sup><xref rid="R6" ref-type="bibr">6</xref></sup> based on 19 index variants with genome-wide significance, 3 with consistent effect direction in the replication stage and 4×10<sup>–7</sup> ≤ P ≤ 2×10<sup>–6</sup>) by selecting (iii) tagging variants (pair-wise tagging r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> < 0.8) from Phase I 1000G/HapMap<sup><xref rid="R52" ref-type="bibr">52</xref>,<xref rid="R53" ref-type="bibr">53</xref></sup> common variants (minor allele frequency, MAF, ≥ 1 % in European or East Asian individuals) using Tagger implemented in Haploview<sup><xref rid="R54" ref-type="bibr">54</xref></sup> within ±100kb of the 22 index variants expanded to cover all correlated variants (r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> [EUR] > 0.5) and the complete gene (transcript ±1 kb), (iv) protein-altering variants within 500 kb of the 22 index variants as identified from public general population data bases (dbSNP<sup><xref rid="R55" ref-type="bibr">55</xref></sup>, the NHLBI Exome Sequencing Project<sup><xref rid="R56" ref-type="bibr">56</xref></sup>, the Phase I 1000 Genomes Project, see <bold>Web Resources</bold>), and (v) protein-altering variants within the 500 kb of the 22 index variants identified by re-sequencing AMD case-control study data (targeted re-sequencing of 2,335 AMD cases and 789 controls<sup><xref rid="R10" ref-type="bibr">10</xref>,<xref rid="R57" ref-type="bibr">57</xref></sup> and whole-genome sequencing 60 AMD cases and 60 controls; G. Abecasis and A. Swaroop). The customization further included (vi) the 1,000 top independent (> 2 Mb distant) variants from the previous analysis and additional 100 top variants from each the previous CNV only and the previous GA only analysis, (vii) and 375 variants in <italic>ABCA4</italic>, including known variants causing Stargardt disease<sup><xref rid="R58" ref-type="bibr">58</xref></sup>, benign variants, and those of unknown significance, as well as 10 known and 44 predicted cysteine mutations in <italic>TIMP3</italic>, motivated by the known variants causing Sorsby's fundus dystrophy<sup><xref rid="R33" ref-type="bibr">33</xref>,<xref rid="R34" ref-type="bibr">34</xref></sup> (also B. Weber, personal communication).</p></sec><sec id="S14"><title>Annotation</title><p id="P30">Variant identifiers were based on NCBI dbSNP v137. Chromosomal position and functional annotation of the variant was based on the NCBI Reference Sequence Human Genome Build 19 (RefSeq hg19)<sup><xref rid="R59" ref-type="bibr">59</xref></sup> and SeattleSeq Annotation 138<sup><xref rid="R60" ref-type="bibr">60</xref></sup> (see <bold>Web Resources</bold>). We particularly focus on protein-altering variants including non-synonymous coding variants (missense, stop loss, in-frame insertion/deletion, frameshift, premature stop codon) and splice sites. We converted the description of splice site variants to HGVS nomenclature using Mutalyzer version 2.0.beta-33<sup><xref rid="R61" ref-type="bibr">61</xref></sup> (see <bold>Web Resources</bold>).</p></sec><sec id="S15"><title>Genotypes</title><p id="P31">We genotyped all subjects centrally at the Center for Inherited Diseases Research (CIDR), Johns Hopkins University School of Medicine, Baltimore, MD, USA. From the 569,645 genotyped variants, our quality control excluded poorly genotyped variants as evidenced by genotype call rates < 98.5% (5.8%), deviations from Hardy-Weinberg equilibrium with P < 10<sup>–6</sup> (0.34%), variants that mapped at multiple genome locations (0.25%) or variants failing other criteria, resulting in 521,950 (91.6%) variants passing all quality criteria. After excluding monomorphic variants (15.8%), we yielded 264,655 common variants distributed across autosomes, sex chromosomes, and mitochondria, as well as 163,714 directly genotyped protein-altering variants including 8,290 from previously implicated AMD loci (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3A</xref>). For these variants, genotype call rates averaged 99.9% (99.1% for subjects with amplified DNA).</p><p id="P32">We phased the autosomal and X-chromosomal genotype data using SHAPEIT (200 states, 2.5 Mb windows)<sup><xref rid="R62" ref-type="bibr">62</xref></sup>, then imputed genotypes based on the 1000 Genomes Project<sup><xref rid="R63" ref-type="bibr">63</xref></sup> reference panel (1000G Phase I, version 3, SHAPEIT2 Reference) using MINIMAC<sup><xref rid="R64" ref-type="bibr">64</xref></sup> (reference-based 2.5 Mb chunks, 500 kb buffer regions). We then merged study variants that were excluded during imputation (not found in the reference panel) back into the final data set. We excluded common variants (CAF ≥ 1%) with bad imputation quality, R<sup><xref rid="R2" ref-type="bibr">2</xref></sup> < 0.3, and adopted a more stringent exclusion criterion for rare variants (CAF < 1%), R<sup><xref rid="R2" ref-type="bibr">2</xref></sup> < 0.8, for the initial identification of lead variants. This yielded a total of 12,023,830 genotyped (439,350) or imputed (11,584,480) quality-controlled variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3A</xref>).</p></sec><sec id="S16" sec-type="subjects"><title>Analyzed subjects</title><p id="P33">Using the genomic information for subject-level quality control, we excluded duplicated and related individuals (kinship coefficient (x003D5) ≥ 0.0884, i.e. 3<sup>rd</sup> degree relatives or closer)<sup><xref rid="R65" ref-type="bibr">65</xref></sup>, subjects with discrepancies between reported gender and sex chromosomal information or with atypical sex chromosome configurations<sup><xref rid="R66" ref-type="bibr">66</xref></sup>, or subjects with genotyping call rates < 98.5%; we derived ancestry based on the first two principal components using autosomal genotyped variants together with genotype information of the samples from the Human Genome Diversity Project (HGDP)<sup><xref rid="R67" ref-type="bibr">67</xref></sup>. Our final data set contained 43,566 successfully genotyped unrelated subjects including 16,144 advanced AMD cases and 17,832 controls of European ancestry, 6,657 intermediate AMD cases of European ancestry, and 2,933 subjects (advanced AMD or controls) of Asian or African ancestries (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3B</xref>).</p></sec><sec id="S17"><title>Genomic heritability and genomic correlation</title><p id="P34">Combined contribution of genotyped variants to disease was evaluated using a variance-component based heritability analysis<sup><xref rid="R68" ref-type="bibr">68</xref></sup>. This analysis used genotypes to build a similarity matrix, summarizing the overall genetic kinship between each pair of individuals, and then examined the correspondence between genetic and phenotypic similarity. We estimated the explained variance on all genotyped, autosomal variants using restricted maximum likelihood (REML) analysis implemented in GCTA<sup><xref rid="R28" ref-type="bibr">28</xref></sup> (see <bold>Web Resources</bold>). We jointly estimated the contributions of rare (MAF in controls < 1 %) and common (MAF in controls ≥ 1%) genotyped variants by first separately calculating their genetic relationship matrices before adding both to the model. Obtained estimates of variance explained were transformed from the observed scale to the liability scale assuming various levels of disease prevalence<sup><xref rid="R68" ref-type="bibr">68</xref></sup>.</p><p id="P35">We estimated the genomic correlation between disease sub-phenotypes using bivariate REML analyses implemented in GCTA and only included common (MAF in controls ≥ 1%) genotyped variants <sup><xref rid="R29" ref-type="bibr">29</xref></sup>. We compared 10,749 cases with CNV versus 3,325 cases with GA (excluding the 2,070 cases with mixed CNV and GA) and we compared 6,657 intermediate AMD cases with 16,144 advanced AMD cases. For both analyses, we used the control subjects as reference and avoided shared controls between traits by randomly splitting the 17,832 unrelated European control individuals into two sub-samples of 8,916 individuals.</p></sec><sec id="S18"><title>Genome-wide single variant association analysis</title><p id="P36">Single-variant association tests analyzing the 16,144 advanced AMD cases and 17,832 controls of European ancestry were based on the Firth bias-corrected likelihood ratio test<sup><xref rid="R69" ref-type="bibr">69</xref></sup>, which is recommended for genetic association studies that include rare variants<sup><xref rid="R70" ref-type="bibr">70</xref></sup>, as implemented in EPACTS (see <bold>Web Resources</bold>). Analyses were adjusted for two principal components and source of DNA (whole-blood or whole-genome amplified DNA). Allele dosages of the imputed data were utilized, Sensitivity analyses were conducted to evaluate the influence of alternative association tests, alternative covariate adjustment including age or sex, or up to 10 principal components instead of two, as well as the influence of restricting to population-based controls, or to controls aged 50 years or older. Genomic control correction<sup><xref rid="R71" ref-type="bibr">71</xref></sup> was used to account for potential population stratification using all genotyped variants with minor allele count ≥ 20 outside of 20 previously described AMD loci<sup><xref rid="R6" ref-type="bibr">6</xref>,<xref rid="R9" ref-type="bibr">9</xref></sup>. As usual for genome-wide association studies, we considered P-values ≤ 5 × 10<sup>–8</sup> as genome-wide significant.</p><p id="P37">To identify independently associated variants, we adopted a sequential forward selection approach: We first computed single variant association for each of the > 12 million variants. Then we selected the variant with the smallest P-value and its flanking ±5 Mb region, repeating the process until no genome-wide significant variant (P ≤ 5 × 10<sup>–8</sup>) was left yielding a number of 10 Mb regions. Within each of these large regions, we re-analyzed each variant conditioning on the top variant, and repeated this process by adding the previously identified genome-wide significant variant(s) within the respective 10 Mb region. This yielded one or more independently associated genome-wide significant variant(s) per 10 Mb region.</p><p id="P38">A locus region was defined by a genome-wide significant variant and its correlated variants (r<sup><xref rid="R2" ref-type="bibr">2</xref></sup>≥ 0.5) ± 500kb; overlapping locus regions were merged to one locus, so some loci contained more than one index variant (details in <xref rid="SD1" ref-type="supplementary-material">Supplementary Figure 3</xref>).</p><p id="P39">In order to derive independent effect sizes (log odds ratios) for all identified variants, we computed a fully conditioned logistic regression model including all identified variants.</p></sec><sec id="S19"><title>Bayesian approach to prioritize variants</title><p id="P40">n order to summarize the statistical evidence of a variant for its association strength, we computed the Bayes factor for each variant, which is a measure of the strength of the association that is comparable irrespective of variant frequency or study sample size. It provides the probability of the genotype configuration at a variant (in cases and controls) under the alternative hypothesis (association) divided by the probability of the genotype configuration under the null hypothesis (no association). It is computed using the association results per variant <sup><xref rid="R72" ref-type="bibr">72</xref></sup>. The posterior probability of each variant is then computed as the Bayes factor relative to the sum of all variants' Bayes factors across one locus region and can be thought of as the relative strength of evidence in favor of each SNP studied in the respective region. This assumes that there is one causal variant per region and that the causal variant is in the analyzed data set.</p><p id="P41">Expanding to loci with multiple association signals and thus a single alleged causal variant per signal, we used the association results per SNP obtained by conditioning on the other independent variants at that locus for computing the Bayes factor.</p><p id="P42">We derived 95% credible sets of variants per signal, which is the minimal set of variants, for which the sum of the posterior probabilities accumulates beyond 95%. This approach was recommended for fine-mapping of association signals and for prioritizing variants<sup><xref rid="R73" ref-type="bibr">73</xref></sup>. Assuming that there is only one causal variant in an association signal and that the causal variant is contained among the analyzed variants, such a credible set of variants contains the causal variant with 95% probability.</p><p id="P43">We annotated functionality of the variants in each of the 95% credible sets (see above).</p></sec><sec id="S20"><title>Gene-based burden analysis</title><p id="P44">Single variant analyses have limited power to depict rare variants with association. Gene-based burden tests evaluating accumulated association from multiple rare variants per gene have been shown to complement such analyses and improve power to detect a burden of disease. We computed the burden of disease using the variable threshold test<sup><xref rid="R51" ref-type="bibr">51</xref></sup> as implemented in EPACTS. These analysis assume that all variants in a gene either increase or decrease disease risk. When variants with opposite directions of effect reside in the same gene, power will be reduced. An analysis with SKAT and SKAT-O, which both allow for variants with opposite directions of effect to reside in the same gene, did not identify additional signals (data not shown).</p><p id="P45">We focused this analysis on protein-altering variants, since we assumed that the other (not protein-altering) variants would outnumber these predicted deleterious variants by far and would thus dilute a disease burden from the deleterious variants. Assuming a negative selection against such deleterious variants that cause their frequency to be low across ancestries, we restricted our rare variant definition to variants with MAF < 1% (cases and controls combined) in each of our ancestry groups (African, Asian, and European). We utilized the genotypes of these rare protein-altering variants if genotyped directly, or rounded imputed allele dosages to the next best genotype if imputed; imputed variants were restricted to those of highest imputation quality (RSQ >= 0.8).</p><p id="P46">We assessed statistical significance by adaptive permutation testing with variable thresholds (up to 100 million permutations; minimal P-value = 1 × 10<sup>–8</sup>)<sup><xref rid="R51" ref-type="bibr">51</xref></sup>. When rare variants appear on a haplotype associated with disease through a common variant allele already identified for AMD, the rare variant burden would depict a mere shadow of the already identified variant. Therefore, we repeated the variable threshold test conditioned on the variant(s) identified in the respective locus by single variant analysis (locus-wide conditioning), to unravel a gene-based burden of rare variants independent of risk variants identified in single variants tests.</p><p id="P47">First, we searched for rare variant disease burden genome-wide applying a genome-wide Bonferroni-corrected significance threshold of 0.05 / 17,044 = 2.9 × 10<sup>–6</sup> (17,044 genes genome-wide with at least 1 variant included in the analysis, i.e. with ≥ 1 rare protein-altering variant). In a second view on this, we focused on our 34 identified AMD loci and here applied a significance threshold based on the 703 genes overlapping with the locus regions (P < 0.05 / 703 = 7.1 × 10<sup>–5</sup>). Odds ratio estimates of the burden were derived by logistic regression using the Wald test on the collapsed burden. As there was an overlap of the sequenced subjects with the chip data subjects, we conducted a sensitivity analysis for the burden test excluding overlapping subjects (see <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 8</xref>).</p></sec><sec id="S21"><title>Follow-up queries for genes underneath the association signals</title><p id="P48">In order to derive information for all genes underneath our 52 identified association signals (spread across the 34 AMD loci), we built a gene list containing all genes that overlapped with a more narrow definition of locus regions: We have been using a particularly comprehensive definition of the locus region during the signal identification step (index variants and proxies, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> ≥ 0.5, ±500kb), to avoid far-reaching linkage disequilibrium that may generate shadow signals (particularly in the light of strong associations in the <italic>CFH</italic>, <italic>C3</italic>, <italic>C2</italic>/<italic>CFI</italic>, and <italic>ARMS2/HTRA1</italic> loci) and to optimally differentiate independent signals within locus. We have also used this wide locus region definition for the rare variant burden test again to fully correct for independent signals in the respective wider locus regions and to be conservative in the multiple testing corrections for the AMD-locus-wide burden test search. However, this wide definition is less adequate when prioritizing genes around the identified signals under the assumption that most protein-altering or regulating variants exert their effects in cis<sup><xref rid="R42" ref-type="bibr">42</xref></sup>. We thus focused the gene list for further queries to a more narrow locus region definition (index variants and proxies, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> ≥ 0.5, ± 100kb) and yield 368 overlapping RefSeq genes (<xref rid="SD1" ref-type="supplementary-material">Supplementary File 5</xref>).</p></sec><sec id="S22"><title>Gene expression</title><p id="P49">For the 368 genes in our gene list (see above), we sought to obtain gene expression in relevant tissues, retina, RPE, and choroid, in two independent data sets (see details in <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 9</xref>). A consensus rating of gene expression observed in the two labs was derived as follows: Expression of a gene in one set of tissues (retina or RPE/choroid) was inferred, if both labs detected expression in the respective set of tissues; if at least one of the labs did not observe expression, the gene was considered as not expressed; gene expression of all other genes (one lab observing expression and the other with missing, or both labs with missing data) was regarded as missing.</p></sec><sec id="S23"><title>Mouse model phenotypes</title><p id="P50">For the 368 genes in our gene list, we queried the Mouse Genome Informatics (MGI)<sup><xref rid="R74" ref-type="bibr">74</xref></sup> and the International Mouse Phenotyping Consortium (IPMC)<sup><xref rid="R75" ref-type="bibr">75</xref></sup> data bases (see <bold>Web Resources</bold>), and manually curated results by information from published literature. We determined whether a gene exhibited a relevant eye-phenotype (i.e. retina, RPE, or choroid phenotypes) in established genetic mouse models (knock-out, knock-in, or trans-genic mice).</p></sec><sec id="S24"><title>Enrichment for molecular pathways</title><p id="P51">For the 368 overlapping genes, we performed functional enrichment analysis using INRICH<sup><xref rid="R76" ref-type="bibr">76</xref></sup> with default settings unless stated otherwise (see <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 10</xref>). Target intervals of this analysis were the narrow AMD locus regions (index variants and proxies, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> ≥ 0.5, ± 100kb, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>). Since there is no consensus approach to pathway analysis, we queried multiple data bases: (i) Kyoto Encyclopedia of Genes and Genomes (KEGG)<sup><xref rid="R77" ref-type="bibr">77</xref></sup>, (ii) Reactome<sup><xref rid="R78" ref-type="bibr">78</xref></sup>, and (iii) Gene Ontology (GO) Consortium<sup><xref rid="R79" ref-type="bibr">79</xref></sup> (see Web Resources). For example, while KEGG is a manually curated database on metabolic pathways, GO also includes automatic annotations and more comprehensive set of cellular processes and molecular functions.</p></sec><sec id="S25"><title>Drug pathways and targets</title><p id="P52">In order to derive information on whether the product of a gene among the 368 genes in our gene list was a direct drug target, we searched the DrugBank database (Version 4.1) which contains 4,207 drug targets (= genes) and 7,740 drugs <sup><xref rid="R80" ref-type="bibr">80</xref></sup>(see <bold>Web Resources</bold>).</p></sec><sec id="S26"><title>Explained variability in disease liability</title><p id="P53">Based on the 52 identified AMD variants, we estimated the explained proportion of disease liability explained by these variants (see <bold>Web Resources</bold>)<sup><xref rid="R81" ref-type="bibr">81</xref></sup> using the log Odds Ratio estimates from the model including all 52 identified variants (fully conditioned) to derive independent effect sizes. We compared this proportion explained by the 52 variants with the earlier derived genomic heritability based on all genotyped variants (see above).</p></sec><sec id="S27"><title>Genetic risk score and relative and absolute genetic risk of AMD</title><p id="P54">For each individual, we computed a genetic risk score (GRS) as the effect size weighted sum of the AMD risk increasing alleles for all 52 independent variants divided by the sum of all effect sizes. To derive a a realistic genetic risk score distribution, we modeled a general population based on our case-control data, which requires an assumption on the prevalence of advanced AMD(see <xref rid="SD1" ref-type="supplementary-material">Supplementary Note 11</xref>). For this modeled general population, we derived the GRS distribution and its deciles. For the weighting, the log Odds Ratios for each of the 52 variants were derived from the fully adjusted model (including all 52 variants) to assure independence of effect sizes.</p><p id="P55">We derived relative risk estimates (as Odds Ratios) for each GRS decile with the first decile as reference. This relative risk estimate is independent of the prevalence except that the decile to form the genetic risk groups used the GRS distribution as expected in a general population (which requires a prevalence assumption). We also computed absolute risk estimates per GRS decile as the proportion of advanced AMD cases applying the weights and prevalence assumptions as described above.</p></sec></sec><sec sec-type="supplementary-material" id="S28"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>1</label><media xlink:href="NIHMS733253-supplement-1.docx" orientation="portrait" xlink:type="simple" id="d37e3336" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD2"><label>2</label><media xlink:href="NIHMS733253-supplement-2.docx" orientation="portrait" xlink:type="simple" id="d37e3340" position="anchor"></media></supplementary-material><supplementary-material content-type="local-data" id="SD3"><label>3</label><media xlink:href="NIHMS733253-supplement-3.doc" orientation="portrait" xlink:type="simple" id="d37e3344" position="anchor"></media></supplementary-material></sec></body><back><ack id="S29"><p>We thank all participants of all the studies included for enabling this research by their participation to these studies. Computer resources for this project have been provided by the High Performance Computing Centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgements can be found in the <xref rid="SD1" ref-type="supplementary-material">Supplementary Note</xref>. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H.</p></ack><ref-list><ref id="R1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Risk factors for age-related macular degeneration: Pooled findings from three continents</article-title><source>Ophthalmology</source><volume>108</volume><fpage>697</fpage><lpage>704</lpage><year>2001</year><pub-id pub-id-type="pmid">11297486</pub-id></element-citation></ref><ref id="R2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chakravarthy</surname><given-names>U</given-names></name><name><surname>Evans</surname><given-names>J</given-names></name><name><surname>Rosenfeld</surname><given-names>PJ</given-names></name></person-group><article-title>Age related macular degeneration</article-title><source>BMJ</source><volume>340</volume><fpage>c981</fpage><year>2010</year><pub-id pub-id-type="pmid">20189972</pub-id></element-citation></ref><ref id="R3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ferris</surname><given-names>FL</given-names></name><etal></etal></person-group><article-title>A simplified severity scale for age-related macular degeneration: AREDS Report No. 18</article-title><source>Arch Ophthalmol</source><volume>123</volume><fpage>1570</fpage><lpage>4</lpage><year>2005</year><pub-id pub-id-type="pmid">16286620</pub-id></element-citation></ref><ref id="R4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wong</surname><given-names>WL</given-names></name><etal></etal></person-group><article-title>Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis</article-title><source>Lancet Glob Health</source><volume>2</volume><fpage>e106</fpage><lpage>16</lpage><year>2014</year><pub-id pub-id-type="pmid">25104651</pub-id></element-citation></ref><ref id="R5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fritsche</surname><given-names>LG</given-names></name><etal></etal></person-group><article-title>Age-related macular degeneration: genetics and biology coming together</article-title><source>Annu Rev Genomics Hum Genet</source><volume>15</volume><fpage>151</fpage><lpage>71</lpage><year>2014</year><pub-id pub-id-type="pmid">24773320</pub-id></element-citation></ref><ref id="R6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fritsche</surname><given-names>LG</given-names></name><etal></etal></person-group><article-title>Seven new loci associated with age-related macular degeneration</article-title><source>Nat Genet</source><volume>45</volume><fpage>433</fpage><lpage>9</lpage><fpage>439e1</fpage><lpage>2</lpage><year>2013</year><pub-id pub-id-type="pmid">23455636</pub-id></element-citation></ref><ref id="R7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Raychaudhuri</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>A rare penetrant mutation in CFH confers high risk of age-related macular degeneration</article-title><source>Nat Genet</source><volume>43</volume><fpage>1232</fpage><lpage>6</lpage><year>2011</year><pub-id pub-id-type="pmid">22019782</pub-id></element-citation></ref><ref id="R8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Helgason</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration</article-title><source>Nat Genet</source><volume>45</volume><fpage>1371</fpage><lpage>4</lpage><year>2013</year><pub-id pub-id-type="pmid">24036950</pub-id></element-citation></ref><ref id="R9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seddon</surname><given-names>JM</given-names></name><etal></etal></person-group><article-title>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration</article-title><source>Nat Genet</source><volume>45</volume><fpage>1366</fpage><lpage>70</lpage><year>2013</year><pub-id pub-id-type="pmid">24036952</pub-id></element-citation></ref><ref id="R10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhan</surname><given-names>X</given-names></name><etal></etal></person-group><article-title>Identification of a rare coding variant in complement 3 associated with age-related macular degeneration</article-title><source>Nat Genet</source><volume>45</volume><fpage>1375</fpage><lpage>9</lpage><year>2013</year><pub-id pub-id-type="pmid">24036949</pub-id></element-citation></ref><ref id="R11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van de Ven</surname><given-names>JP</given-names></name><etal></etal></person-group><article-title>A functional variant in the CFI gene confers a high risk of age-related macular degeneration</article-title><source>Nat Genet</source><volume>45</volume><fpage>813</fpage><lpage>7</lpage><year>2013</year><pub-id pub-id-type="pmid">23685748</pub-id></element-citation></ref><ref id="R12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arakawa</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population</article-title><source>Nat Genet</source><volume>43</volume><fpage>1001</fpage><lpage>4</lpage><year>2011</year><pub-id pub-id-type="pmid">21909106</pub-id></element-citation></ref><ref id="R13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gibson</surname><given-names>G</given-names></name></person-group><article-title>Rare and common variants: twenty arguments</article-title><source>Nat Rev Genet</source><volume>13</volume><fpage>135</fpage><lpage>45</lpage><year>2011</year><pub-id pub-id-type="pmid">22251874</pub-id></element-citation></ref><ref id="R14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Do</surname><given-names>R</given-names></name><name><surname>Kathiresan</surname><given-names>S</given-names></name><name><surname>Abecasis</surname><given-names>GR</given-names></name></person-group><article-title>Exome sequencing and complex disease: practical aspects of rare variant association studies</article-title><source>Hum Mol Genet</source><volume>21</volume><fpage>R1</fpage><lpage>9</lpage><year>2012</year><pub-id pub-id-type="pmid">22983955</pub-id></element-citation></ref><ref id="R15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nelson</surname><given-names>MR</given-names></name><etal></etal></person-group><article-title>An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people</article-title><source>Science</source><volume>337</volume><fpage>100</fpage><lpage>4</lpage><year>2012</year><pub-id pub-id-type="pmid">22604722</pub-id></element-citation></ref><ref id="R16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zuk</surname><given-names>O</given-names></name><etal></etal></person-group><article-title>Searching for missing heritability: designing rare variant association studies</article-title><source>Proc Natl Acad Sci U S A</source><volume>111</volume><fpage>E455</fpage><lpage>64</lpage><year>2014</year><pub-id pub-id-type="pmid">24443550</pub-id></element-citation></ref><ref id="R17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vogelstein</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Cancer genome landscapes</article-title><source>Science</source><volume>339</volume><fpage>1546</fpage><lpage>58</lpage><year>2013</year><pub-id pub-id-type="pmid">23539594</pub-id></element-citation></ref><ref id="R18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Styrkarsdottir</surname><given-names>U</given-names></name><etal></etal></person-group><article-title>Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31</article-title><source>Nat Genet</source><volume>46</volume><fpage>498</fpage><lpage>502</lpage><year>2014</year><pub-id pub-id-type="pmid">24728293</pub-id></element-citation></ref><ref id="R19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Styrkarsdottir</surname><given-names>U</given-names></name><etal></etal></person-group><article-title>Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits</article-title><source>Nature</source><volume>497</volume><fpage>517</fpage><lpage>20</lpage><year>2013</year><pub-id pub-id-type="pmid">23644456</pub-id></element-citation></ref><ref id="R20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rivas</surname><given-names>MA</given-names></name><etal></etal></person-group><article-title>Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease</article-title><source>Nat Genet</source><volume>43</volume><fpage>1066</fpage><lpage>73</lpage><year>2011</year><pub-id pub-id-type="pmid">21983784</pub-id></element-citation></ref><ref id="R21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Flannick</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Loss-of-function mutations in SLC30A8 protect against type 2 diabetes</article-title><source>Nat Genet</source><volume>46</volume><fpage>357</fpage><lpage>63</lpage><year>2014</year><pub-id pub-id-type="pmid">24584071</pub-id></element-citation></ref><ref id="R22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cruchaga</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease</article-title><source>Nature</source><volume>505</volume><fpage>550</fpage><lpage>4</lpage><year>2014</year><pub-id pub-id-type="pmid">24336208</pub-id></element-citation></ref><ref id="R23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Do</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction</article-title><source>Nature</source><volume>518</volume><fpage>102</fpage><lpage>6</lpage><year>2015</year><pub-id pub-id-type="pmid">25487149</pub-id></element-citation></ref><ref id="R24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lange</surname><given-names>LA</given-names></name><etal></etal></person-group><article-title>Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol</article-title><source>Am J Hum Genet</source><volume>94</volume><fpage>233</fpage><lpage>45</lpage><year>2014</year><pub-id pub-id-type="pmid">24507775</pub-id></element-citation></ref><ref id="R25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walters</surname><given-names>RG</given-names></name><etal></etal></person-group><article-title>A new highly penetrant form of obesity due to deletions on chromosome 16p11.2</article-title><source>Nature</source><volume>463</volume><fpage>671</fpage><lpage>5</lpage><year>2010</year><pub-id pub-id-type="pmid">20130649</pub-id></element-citation></ref><ref id="R26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Locke</surname><given-names>AE</given-names></name><etal></etal></person-group><article-title>Genetic studies of body mass index yield new insights for obesity biology</article-title><source>Nature</source><volume>518</volume><fpage>197</fpage><lpage>206</lpage><year>2015</year><pub-id pub-id-type="pmid">25673413</pub-id></element-citation></ref><ref id="R27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shungin</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>New genetic loci link adipose and insulin biology to body fat distribution</article-title><source>Nature</source><volume>518</volume><fpage>187</fpage><lpage>96</lpage><year>2015</year><pub-id pub-id-type="pmid">25673412</pub-id></element-citation></ref><ref id="R28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Lee</surname><given-names>SH</given-names></name><name><surname>Goddard</surname><given-names>ME</given-names></name><name><surname>Visscher</surname><given-names>PM</given-names></name></person-group><article-title>GCTA: a tool for genome-wide complex trait analysis</article-title><source>Am J Hum Genet</source><volume>88</volume><fpage>76</fpage><lpage>82</lpage><year>2011</year><pub-id pub-id-type="pmid">21167468</pub-id></element-citation></ref><ref id="R29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>SH</given-names></name><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Goddard</surname><given-names>ME</given-names></name><name><surname>Visscher</surname><given-names>PM</given-names></name><name><surname>Wray</surname><given-names>NR</given-names></name></person-group><article-title>Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood</article-title><source>Bioinformatics</source><volume>28</volume><fpage>2540</fpage><lpage>2</lpage><year>2012</year><pub-id pub-id-type="pmid">22843982</pub-id></element-citation></ref><ref id="R30"><label>30</label><element-citation publication-type="journal"><collab>Wellcome Trust Case Control, C</collab><etal></etal><article-title>Bayesian refinement of association signals for 14 loci in 3 common diseases</article-title><source>Nat Genet</source><volume>44</volume><fpage>1294</fpage><lpage>301</lpage><year>2012</year><pub-id pub-id-type="pmid">23104008</pub-id></element-citation></ref><ref id="R31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wen</surname><given-names>X</given-names></name></person-group><article-title>Bayesian model selection in complex linear systems, as illustrated in genetic association studies</article-title><source>Biometrics</source><volume>70</volume><fpage>73</fpage><lpage>83</lpage><year>2014</year><pub-id pub-id-type="pmid">24350677</pub-id></element-citation></ref><ref id="R32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nejentsev</surname><given-names>S</given-names></name><name><surname>Walker</surname><given-names>N</given-names></name><name><surname>Riches</surname><given-names>D</given-names></name><name><surname>Egholm</surname><given-names>M</given-names></name><name><surname>Todd</surname><given-names>JA</given-names></name></person-group><article-title>Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes</article-title><source>Science</source><volume>324</volume><fpage>387</fpage><lpage>9</lpage><year>2009</year><pub-id pub-id-type="pmid">19264985</pub-id></element-citation></ref><ref id="R33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sorsby</surname><given-names>A</given-names></name><name><surname>Mason</surname><given-names>ME</given-names></name></person-group><article-title>A fundus dystrophy with unusual features</article-title><source>Br J Ophthalmol</source><volume>33</volume><fpage>67</fpage><lpage>97</lpage><year>1949</year><pub-id pub-id-type="pmid">18111349</pub-id></element-citation></ref><ref id="R34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weber</surname><given-names>BH</given-names></name><name><surname>Vogt</surname><given-names>G</given-names></name><name><surname>Wolz</surname><given-names>W</given-names></name><name><surname>Ives</surname><given-names>EJ</given-names></name><name><surname>Ewing</surname><given-names>CC</given-names></name></person-group><article-title>Sorsby's fundus dystrophy is genetically linked to chromosome 22q13-qter</article-title><source>Nat Genet</source><volume>7</volume><fpage>158</fpage><lpage>61</lpage><year>1994</year><pub-id pub-id-type="pmid">7920634</pub-id></element-citation></ref><ref id="R35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abecasis</surname><given-names>GR</given-names></name><etal></etal></person-group><article-title>Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease</article-title><source>Am J Hum Genet</source><volume>74</volume><fpage>482</fpage><lpage>94</lpage><year>2004</year><pub-id pub-id-type="pmid">14968411</pub-id></element-citation></ref><ref id="R36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Speliotes</surname><given-names>EK</given-names></name><etal></etal></person-group><article-title>Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index</article-title><source>Nat Genet</source><volume>42</volume><fpage>937</fpage><lpage>48</lpage><year>2010</year><pub-id pub-id-type="pmid">20935630</pub-id></element-citation></ref><ref id="R37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kottgen</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>New loci associated with kidney function and chronic kidney disease</article-title><source>Nat Genet</source><volume>42</volume><fpage>376</fpage><lpage>84</lpage><year>2010</year><pub-id pub-id-type="pmid">20383146</pub-id></element-citation></ref><ref id="R38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Allikmets</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration</article-title><source>Science</source><volume>277</volume><fpage>1805</fpage><lpage>7</lpage><year>1997</year><pub-id pub-id-type="pmid">9295268</pub-id></element-citation></ref><ref id="R39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Halestrap</surname><given-names>AP</given-names></name></person-group><article-title>The SLC16 gene family - structure, role and regulation in health and disease</article-title><source>Mol Aspects Med</source><volume>34</volume><fpage>337</fpage><lpage>49</lpage><year>2013</year><pub-id pub-id-type="pmid">23506875</pub-id></element-citation></ref><ref id="R40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Daniele</surname><given-names>LL</given-names></name><name><surname>Sauer</surname><given-names>B</given-names></name><name><surname>Gallagher</surname><given-names>SM</given-names></name><name><surname>Pugh</surname><given-names>EN</given-names><suffix>Jr</suffix></name><name><surname>Philp</surname><given-names>NJ</given-names></name></person-group><article-title>Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice</article-title><source>Am J Physiol Cell Physiol</source><volume>295</volume><fpage>C451</fpage><lpage>7</lpage><year>2008</year><pub-id pub-id-type="pmid">18524945</pub-id></element-citation></ref><ref id="R41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shoshan</surname><given-names>V</given-names></name><name><surname>MacLennan</surname><given-names>DH</given-names></name><name><surname>Wood</surname><given-names>DS</given-names></name></person-group><article-title>A proton gradient controls a calcium-release channel in sarcoplasmic reticulum</article-title><source>Proc Natl Acad Sci U S A</source><volume>78</volume><fpage>4828</fpage><lpage>32</lpage><year>1981</year><pub-id pub-id-type="pmid">6272276</pub-id></element-citation></ref><ref id="R42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stranger</surname><given-names>BE</given-names></name><etal></etal></person-group><article-title>Patterns of cis regulatory variation in diverse human populations</article-title><source>PLoS Genet</source><volume>8</volume><fpage>e1002639</fpage><year>2012</year><pub-id pub-id-type="pmid">22532805</pub-id></element-citation></ref><ref id="R43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lambert</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane</article-title><source>Arthritis Rheumatol</source><volume>66</volume><fpage>960</fpage><lpage>8</lpage><year>2014</year><pub-id pub-id-type="pmid">24757147</pub-id></element-citation></ref><ref id="R44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hollborn</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Positive feedback regulation between MMP-9 and VEGF in human RPE cells</article-title><source>Invest Ophthalmol Vis Sci</source><volume>48</volume><fpage>4360</fpage><lpage>7</lpage><year>2007</year><pub-id pub-id-type="pmid">17724228</pub-id></element-citation></ref><ref id="R45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rudnicka</surname><given-names>AR</given-names></name><etal></etal></person-group><article-title>Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis</article-title><source>Ophthalmology</source><volume>119</volume><fpage>571</fpage><lpage>80</lpage><year>2012</year><pub-id pub-id-type="pmid">22176800</pub-id></element-citation></ref><ref id="R46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration</article-title><source>Proc Natl Acad Sci U S A</source><volume>107</volume><fpage>7401</fpage><lpage>6</lpage><year>2010</year><pub-id pub-id-type="pmid">20385819</pub-id></element-citation></ref><ref id="R47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Logue</surname><given-names>MW</given-names></name><etal></etal></person-group><article-title>A search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways</article-title><source>Neurobiol Aging</source><volume>35</volume><fpage>1510.e7</fpage><lpage>18</lpage><year>2014</year><pub-id pub-id-type="pmid">24439028</pub-id></element-citation></ref><ref id="R48"><label>48</label><element-citation publication-type="journal"><collab>The Encode Project Consortium</collab><article-title>An integrated encyclopedia of DNA elements in the human genome</article-title><source>Nature</source><volume>489</volume><fpage>57</fpage><lpage>74</lpage><year>2012</year><pub-id pub-id-type="pmid">22955616</pub-id></element-citation></ref><ref id="R49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hussain</surname><given-names>AA</given-names></name><name><surname>Lee</surname><given-names>Y</given-names></name><name><surname>Zhang</surname><given-names>JJ</given-names></name><name><surname>Marshall</surname><given-names>J</given-names></name></person-group><article-title>Disturbed matrix metalloproteinase activity of Bruch's membrane in age-related macular degeneration</article-title><source>Invest Ophthalmol Vis Sci</source><volume>52</volume><fpage>4459</fpage><lpage>66</lpage><year>2011</year><pub-id pub-id-type="pmid">21498613</pub-id></element-citation></ref><ref id="R50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johansen</surname><given-names>CT</given-names></name><etal></etal></person-group><article-title>Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia</article-title><source>Nat Genet</source><volume>42</volume><fpage>684</fpage><lpage>7</lpage><year>2010</year><pub-id pub-id-type="pmid">20657596</pub-id></element-citation></ref><ref id="R51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Price</surname><given-names>AL</given-names></name><etal></etal></person-group><article-title>Pooled association tests for rare variants in exon-resequencing studies</article-title><source>Am J Hum Genet</source><volume>86</volume><fpage>832</fpage><lpage>8</lpage><year>2010</year><pub-id pub-id-type="pmid">20471002</pub-id></element-citation></ref><ref id="R52"><label>52</label><element-citation publication-type="journal"><collab>The International Hapmap Consortium</collab><etal></etal><article-title>A second generation human haplotype map of over 3.1 million SNPs</article-title><source>Nature</source><volume>449</volume><fpage>851</fpage><lpage>61</lpage><year>2007</year><pub-id pub-id-type="pmid">17943122</pub-id></element-citation></ref><ref id="R53"><label>53</label><element-citation publication-type="journal"><collab>1000 Genomes Project Consortium</collab><etal></etal><article-title>An integrated map of genetic variation from 1,092 human genomes</article-title><source>Nature</source><volume>491</volume><fpage>56</fpage><lpage>65</lpage><year>2012</year><pub-id pub-id-type="pmid">23128226</pub-id></element-citation></ref><ref id="R54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barrett</surname><given-names>JC</given-names></name><name><surname>Fry</surname><given-names>B</given-names></name><name><surname>Maller</surname><given-names>J</given-names></name><name><surname>Daly</surname><given-names>MJ</given-names></name></person-group><article-title>Haploview: analysis and visualization of LD and haplotype maps</article-title><source>Bioinformatics</source><volume>21</volume><fpage>263</fpage><lpage>5</lpage><year>2005</year><pub-id pub-id-type="pmid">15297300</pub-id></element-citation></ref><ref id="R55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sherry</surname><given-names>ST</given-names></name><etal></etal></person-group><article-title>dbSNP: the NCBI database of genetic variation</article-title><source>Nucleic Acids Res</source><volume>29</volume><fpage>308</fpage><lpage>11</lpage><year>2001</year><pub-id pub-id-type="pmid">11125122</pub-id></element-citation></ref><ref id="R56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tennessen</surname><given-names>JA</given-names></name><etal></etal></person-group><article-title>Evolution and functional impact of rare coding variation from deep sequencing of human exomes</article-title><source>Science</source><volume>337</volume><fpage>64</fpage><lpage>9</lpage><year>2012</year><pub-id pub-id-type="pmid">22604720</pub-id></element-citation></ref><ref id="R57"><label>57</label><element-citation publication-type="journal"><collab>Age-Related Eye Disease Study Research, G</collab><article-title>A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9</article-title><source>Arch Ophthalmol</source><volume>119</volume><fpage>1439</fpage><lpage>52</lpage><year>2001</year><pub-id pub-id-type="pmid">11594943</pub-id></element-citation></ref><ref id="R58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fritsche</surname><given-names>LG</given-names></name><etal></etal></person-group><article-title>A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene</article-title><source>Invest Ophthalmol Vis Sci</source><volume>53</volume><fpage>2112</fpage><lpage>8</lpage><year>2012</year><pub-id pub-id-type="pmid">22427542</pub-id></element-citation></ref><ref id="R59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pruitt</surname><given-names>KD</given-names></name><etal></etal></person-group><article-title>RefSeq: an update on mammalian reference sequences</article-title><source>Nucleic Acids Res</source><volume>42</volume><fpage>D756</fpage><lpage>63</lpage><year>2014</year><pub-id pub-id-type="pmid">24259432</pub-id></element-citation></ref><ref id="R60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ng</surname><given-names>SB</given-names></name><etal></etal></person-group><article-title>Targeted capture and massively parallel sequencing of 12 human exomes</article-title><source>Nature</source><volume>461</volume><fpage>272</fpage><lpage>6</lpage><year>2009</year><pub-id pub-id-type="pmid">19684571</pub-id></element-citation></ref><ref id="R61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wildeman</surname><given-names>M</given-names></name><name><surname>van Ophuizen</surname><given-names>E</given-names></name><name><surname>den Dunnen</surname><given-names>JT</given-names></name><name><surname>Taschner</surname><given-names>PE</given-names></name></person-group><article-title>Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker</article-title><source>Hum Mutat</source><volume>29</volume><fpage>6</fpage><lpage>13</lpage><year>2008</year><pub-id pub-id-type="pmid">18000842</pub-id></element-citation></ref><ref id="R62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delaneau</surname><given-names>O</given-names></name><name><surname>Marchini</surname><given-names>J</given-names></name><name><surname>Zagury</surname><given-names>JF</given-names></name></person-group><article-title>A linear complexity phasing method for thousands of genomes</article-title><source>Nat Methods</source><volume>9</volume><fpage>179</fpage><lpage>81</lpage><year>2012</year><pub-id pub-id-type="pmid">22138821</pub-id></element-citation></ref><ref id="R63"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ristau</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Allergy is a protective factor against age-related macular degeneration</article-title><source>Invest Ophthalmol Vis Sci</source><volume>55</volume><fpage>210</fpage><lpage>4</lpage><year>2014</year><pub-id pub-id-type="pmid">24235017</pub-id></element-citation></ref><ref id="R64"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Howie</surname><given-names>B</given-names></name><name><surname>Fuchsberger</surname><given-names>C</given-names></name><name><surname>Stephens</surname><given-names>M</given-names></name><name><surname>Marchini</surname><given-names>J</given-names></name><name><surname>Abecasis</surname><given-names>GR</given-names></name></person-group><article-title>Fast and accurate genotype imputation in genome-wide association studies through pre-phasing</article-title><source>Nat Genet</source><volume>44</volume><fpage>955</fpage><lpage>9</lpage><year>2012</year><pub-id pub-id-type="pmid">22820512</pub-id></element-citation></ref><ref id="R65"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Manichaikul</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Robust relationship inference in genome-wide association studies</article-title><source>Bioinformatics</source><volume>26</volume><fpage>2867</fpage><lpage>73</lpage><year>2010</year><pub-id pub-id-type="pmid">20926424</pub-id></element-citation></ref><ref id="R66"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Turner</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Quality control procedures for genome-wide association studies</article-title><source>Curr Protoc Hum Genet</source><volume>Chapter 1</volume><comment>Unit1</comment><fpage>19</fpage><year>2011</year><pub-id pub-id-type="pmid">21234875</pub-id></element-citation></ref><ref id="R67"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cavalli-Sforza</surname><given-names>LL</given-names></name></person-group><article-title>The Human Genome Diversity Project: past, present and future</article-title><source>Nat Rev Genet</source><volume>6</volume><fpage>333</fpage><lpage>40</lpage><year>2005</year><pub-id pub-id-type="pmid">15803201</pub-id></element-citation></ref><ref id="R68"><label>68</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>SH</given-names></name><name><surname>Wray</surname><given-names>NR</given-names></name><name><surname>Goddard</surname><given-names>ME</given-names></name><name><surname>Visscher</surname><given-names>PM</given-names></name></person-group><article-title>Estimating missing heritability for disease from genome-wide association studies</article-title><source>Am J Hum Genet</source><volume>88</volume><fpage>294</fpage><lpage>305</lpage><year>2011</year><pub-id pub-id-type="pmid">21376301</pub-id></element-citation></ref><ref id="R69"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Firth</surname><given-names>D</given-names></name></person-group><article-title>Bias reduction of maximum likelihood estimates</article-title><source>Biometrika</source><volume>80</volume><fpage>27</fpage><lpage>38</lpage><year>1993</year></element-citation></ref><ref id="R70"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ma</surname><given-names>C</given-names></name><name><surname>Blackwell</surname><given-names>T</given-names></name><name><surname>Boehnke</surname><given-names>M</given-names></name><name><surname>Scott</surname><given-names>LJ</given-names></name><name><surname>Go</surname><given-names>TDi</given-names></name></person-group><article-title>Recommended joint and meta-analysis strategies for case-control association testing of single low-count variants</article-title><source>Genet Epidemiol</source><volume>37</volume><fpage>539</fpage><lpage>50</lpage><year>2013</year><pub-id pub-id-type="pmid">23788246</pub-id></element-citation></ref><ref id="R71"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devlin</surname><given-names>B</given-names></name><name><surname>Roeder</surname><given-names>K</given-names></name></person-group><article-title>Genomic control for association studies</article-title><source>Biometrics</source><volume>55</volume><fpage>997</fpage><lpage>1004</lpage><year>1999</year><pub-id pub-id-type="pmid">11315092</pub-id></element-citation></ref><ref id="R72"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stephens</surname><given-names>M</given-names></name><name><surname>Balding</surname><given-names>DJ</given-names></name></person-group><article-title>Bayesian statistical methods for genetic association studies</article-title><source>Nat Rev Genet</source><volume>10</volume><fpage>681</fpage><lpage>90</lpage><year>2009</year><pub-id pub-id-type="pmid">19763151</pub-id></element-citation></ref><ref id="R73"><label>73</label><element-citation publication-type="journal"><collab>Wellcome Trust Case Control Consortium</collab><etal></etal><article-title>Bayesian refinement of association signals for 14 loci in 3 common diseases</article-title><source>Nat Genet</source><volume>44</volume><fpage>1294</fpage><lpage>301</lpage><year>2012</year><pub-id pub-id-type="pmid">23104008</pub-id></element-citation></ref><ref id="R74"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blake</surname><given-names>JA</given-names></name><name><surname>Bult</surname><given-names>CJ</given-names></name><name><surname>Eppig</surname><given-names>JT</given-names></name><name><surname>Kadin</surname><given-names>JA</given-names></name><name><surname>Richardson</surname><given-names>JE</given-names></name></person-group><article-title>The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse</article-title><source>Nucleic Acids Res</source><volume>42</volume><fpage>D810</fpage><lpage>7</lpage><year>2014</year><pub-id pub-id-type="pmid">24285300</pub-id></element-citation></ref><ref id="R75"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname><given-names>SD</given-names></name><name><surname>Moore</surname><given-names>MW</given-names></name></person-group><article-title>Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium</article-title><source>Dis Model Mech</source><volume>5</volume><fpage>289</fpage><lpage>92</lpage><year>2012</year><pub-id pub-id-type="pmid">22566555</pub-id></element-citation></ref><ref id="R76"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>PH</given-names></name><name><surname>O'Dushlaine</surname><given-names>C</given-names></name><name><surname>Thomas</surname><given-names>B</given-names></name><name><surname>Purcell</surname><given-names>SM</given-names></name></person-group><article-title>INRICH: interval-based enrichment analysis for genome-wide association studies</article-title><source>Bioinformatics</source><volume>28</volume><fpage>1797</fpage><lpage>9</lpage><year>2012</year><pub-id pub-id-type="pmid">22513993</pub-id></element-citation></ref><ref id="R77"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kanehisa</surname><given-names>M</given-names></name><name><surname>Goto</surname><given-names>S</given-names></name></person-group><article-title>KEGG: kyoto encyclopedia of genes and genomes</article-title><source>Nucleic Acids Res</source><volume>28</volume><fpage>27</fpage><lpage>30</lpage><year>2000</year><pub-id pub-id-type="pmid">10592173</pub-id></element-citation></ref><ref id="R78"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Croft</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>The Reactome pathway knowledgebase</article-title><source>Nucleic Acids Res</source><volume>42</volume><fpage>D472</fpage><lpage>7</lpage><year>2014</year><pub-id pub-id-type="pmid">24243840</pub-id></element-citation></ref><ref id="R79"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ashburner</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Gene ontology: tool for the unification of biology. The Gene Ontology Consortium</article-title><source>Nat Genet</source><volume>25</volume><fpage>25</fpage><lpage>9</lpage><year>2000</year><pub-id pub-id-type="pmid">10802651</pub-id></element-citation></ref><ref id="R80"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Law</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>DrugBank 4.0: shedding new light on drug metabolism</article-title><source>Nucleic Acids Res</source><volume>42</volume><fpage>D1091</fpage><lpage>7</lpage><year>2014</year><pub-id pub-id-type="pmid">24203711</pub-id></element-citation></ref><ref id="R81"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>So</surname><given-names>HC</given-names></name><name><surname>Gui</surname><given-names>AH</given-names></name><name><surname>Cherny</surname><given-names>SS</given-names></name><name><surname>Sham</surname><given-names>PC</given-names></name></person-group><article-title>Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases</article-title><source>Genet Epidemiol</source><volume>35</volume><fpage>310</fpage><lpage>7</lpage><year>2011</year><pub-id pub-id-type="pmid">21374718</pub-id></element-citation></ref></ref-list><app-group><app id="APP1"><title>Web Resources</title><p id="P56"><bold>Full GWAS results</bold>: <ext-link ext-link-type="uri" xlink:href="http://amdgenetics.org/">http://amdgenetics.org/</ext-link></p><p id="P57">The following Web Resources have been utilized:</p><p id="P58">GWAS catalog <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/gwas/home">http://www.ebi.ac.uk/gwas/home</ext-link>),</p><p id="P59">Exome Variant Server, NHLBI GO Exome Sequencing Project:</p><p id="P60"><ext-link ext-link-type="uri" xlink:href="http://evs.gs.washington.edu/EVS/">http://evs.gs.washington.edu/EVS/</ext-link></p><p id="P61">EPACTS: <ext-link ext-link-type="uri" xlink:href="http://www.sph.umich.edu/csg/kang/epacts/index.html">http://www.sph.umich.edu/csg/kang/epacts/index.html</ext-link></p><p id="P62">SHAPEIT: <ext-link ext-link-type="uri" xlink:href="https://mathgen.stats.ox.ac.uk/genetics_software/shapeit/shapeit.html">https://mathgen.stats.ox.ac.uk/genetics_software/shapeit/shapeit.html</ext-link></p><p id="P63">MINIMAC: <ext-link ext-link-type="uri" xlink:href="http://genome.sph.umich.edu/wiki/Minimac">http://genome.sph.umich.edu/wiki/Minimac</ext-link></p><p id="P64">1000 Genomes Reference Panel:</p><p id="P65"><ext-link ext-link-type="uri" xlink:href="http://www.sph.umich.edu/csg/abecasis/MACH/download/1000G.2013-09.html">http://www.sph.umich.edu/csg/abecasis/MACH/download/1000G.2013-09.html</ext-link></p><p id="P66">The Human Genome Diversity Project data:</p><p id="P67"><ext-link ext-link-type="uri" xlink:href="http://genome.sph.umich.edu/wiki/LASER">http://genome.sph.umich.edu/wiki/LASER</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://www.hagsc.org/hgdp">http://www.hagsc.org/hgdp</ext-link></p><p id="P68">SeattleSeq: <ext-link ext-link-type="uri" xlink:href="http://snp.gs.washington.edu/SeattleSeqAnnotation138/index.jsp">http://snp.gs.washington.edu/SeattleSeqAnnotation138/index.jsp</ext-link></p><p id="P69">Mutalyzer: <ext-link ext-link-type="uri" xlink:href="https://mutalyzer.nl">https://mutalyzer.nl</ext-link></p><p id="P70">NCBI Reference Sequence (RefSeq, downloaded December, 2012):</p><p id="P71"><ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/refseq/">http://www.ncbi.nlm.nih.gov/refseq/</ext-link></p><p id="P72">Human Splicing Finder 3.0: <ext-link ext-link-type="uri" xlink:href="http://www.umd.be/HSF3/index.html">http://www.umd.be/HSF3/index.html</ext-link></p><p id="P73">PubMed (retrieved November 11, 2014): <ext-link ext-link-type="uri" xlink:href="http://www.pubmed.org">http://www.pubmed.org</ext-link></p><p id="P74">Mouse Genome Informatics (MGI) databases: <ext-link ext-link-type="uri" xlink:href="http://www.informatics.jax.org">http://www.informatics.jax.org</ext-link></p><p id="P75">International Mouse Phenotyping Consortium Database: <ext-link ext-link-type="uri" xlink:href="https://www.mousephenotype.org">https://www.mousephenotype.org</ext-link></p><p id="P76">INRICH: <ext-link ext-link-type="uri" xlink:href="http://atgu.mgh.harvard.edu/inrich/">http://atgu.mgh.harvard.edu/inrich/</ext-link></p><p id="P77">KEGG: Kyoto Encyclopedia of Genes and Genomes (KEGG): <ext-link ext-link-type="uri" xlink:href="http://www.genome.jp/kegg/">http://www.genome.jp/kegg/</ext-link></p><p id="P78">MSigDB database v4.0: <ext-link ext-link-type="uri" xlink:href="http://www.broadinstitute.org/gsea/index.jsp">http://www.broadinstitute.org/gsea/index.jsp</ext-link></p><p id="P79">Reactome (downloaded January 12th, 2015): <ext-link ext-link-type="uri" xlink:href="http://www.reactome.org">http://www.reactome.org</ext-link></p><p id="P80">Gene Ontology (GO) Consortium (downloaded January 12th, 2015): <ext-link ext-link-type="uri" xlink:href="http://geneontology.org">http://geneontology.org</ext-link></p><p id="P81">DrugBank (downloaded June 4, 2014): <ext-link ext-link-type="uri" xlink:href="http://www.drugbank.ca">http://www.drugbank.ca</ext-link></p><p id="P82">GCTA: <ext-link ext-link-type="uri" xlink:href="http://www.complextraitgenomics.com/software/gcta/">http://www.complextraitgenomics.com/software/gcta/</ext-link></p><p id="P83">Variance explained by genetic variants: <ext-link ext-link-type="uri" xlink:href="https://sites.google.com/site/honcheongso/software/varexp">https://sites.google.com/site/honcheongso/software/varexp</ext-link></p></app><app id="APP2"><title>Author Contributions</title><p id="P84"><bold>Clinical Ascertainment, Contribution of Samples, Study Coordination, and Data Analysis:</bold> Gonçalo R. Abecasis, Anita Agarwal, Jeeyun Ahn, Rando Allikmets, Isabelle Audo, Paul N. Baird, Elisa Bala, Mustapha Benchaboune, Hélène Blanché, John Blangero, Frédéric Blon, Alexis Boleda, Caroline Brandl, Kari E. Branham, Murray H. Brilliant, Kathryn P. Burdon, Melinda S. Cain, Peter Campochiaro, Albert Caramoy, Daniel Chen, David Cho, Itay Chowers, Ian J. Constable, Jamie E. Craig, Angela Cree, Christine Curcio, Margaret DeAngelis, Jean-François Deleuze, Anneke I. den Hollander, Bal Dhillon, Lebriz Ersoy, Lindsay A. Farrer, Sascha Fauser, Henry Ferreyra, Ken Flagg, Johanna R. Foerster, Lars G. Fritsche, Linn Gieser, Bamini Gopinath, Michael B. Gorin, Srinivas Goverdhan, Robyn H. Guymer, Shira Hagbi-Levi, Stephanie A. Hagstrom, Jonathan L. Haines, Janette Hall, Michael A. Hauser, Caroline Hayward, Scott J. Hebbring, John R. Heckenlively, Iris M. Heid, Alex W. Hewitt, Joshua D. Hoffman, Frank G. Holz, Carel B. Hoyng, David J. Hunter, Timothy Isaacs, Sudha K. Iyengar, Matthew P. Johnson, Nicholas Katsanis, Jane Khan, Ivana K. Kim, Terrie E. Kitchner, Caroline C. W. Klaver, Barbara E. K. Klein, Michael L. Klein, Ronald Klein, Jaclyn L. Kovach, Alan M. Kwong, Stewart Lake, Thomas Langmann, Reneé Laux, Yara T. E. Lechanteur, Kristine E. Lee, Thierry Léveillard, Mingyao Li, Helena Hai Liang, Gerald Liew, Danni Lin, Andrew Lotery, Hongrong Luo, David A. Mackey, Guanping Mao, Tammy M. Martin, Ian L. McAllister, J. Allie McGrath, Joanna E. Merriam, John C. Merriam, Stacy M. Meuer, Paul Mitchell, Saddek Mohand-Saïd, Anthony T. Moore, Emily L. Moore, Chelsea E. Myers, Anton Orlin, Mohammad I. Othman, Hong Ouyang, Kyu Hyung Park, Neal S. Peachey, Margaret A. Pericak-Vance, Eric A. Postel, Christina Rennie, Andrea J. Richardson, Guenther Rudolph, José-Alain Sahel, Nicole T. M. Saksens, Debra A. Schaumberg, Tina Schick, Hendrik P. N. Scholl, Stephen G. Schwartz, William K. Scott, Sebanti Sengupta, Humma Shahid, Giuliana Silvestri, R. Theodore Smith, Eric Souied, Emmanuelle Souzeau, Dwight Stambolian, Zhiguang Su, Anand Swaroop, Ava G. Tan, Barbara Truitt, Evangelia E. Tsironi, Cornelia M. van Duijn, Claudia N. von Strachwitz, Brendan J. Vote, Jie Jin Wang, Bernhard H. F. Weber, Daniel E. Weeks, Cindy Wen, Armin Wolf, Zhenglin Yang, John R. W. Yates, Donald Zack, Kang Zhang</p><p id="P85"><bold>Phenotype Committee:</bold> Ivana K. Kim (lead), Sudha K. Iyengar (lead), Margaret DeAngelis (lead), Gabriëlle H. S. Buitendijk, Emily Y. Chew, Itay Chowers, Anneke I. den Hollander, Sascha Fauser, Michael B. Gorin, Jonathan L. Haines, Iris M. Heid, Alex W. Hewitt, Caroline C. W. Klaver, Barbara E. K. Klein, Michael L. Klein, Ronald Klein, Thierry Léveillard, Andrew Lotery, Kyu Hyung Park, Jie Jin Wang, Kang Zhang</p></app><app id="APP3"><title>Data Analysis</title><p id="P86"><italic>Team 1: Quality control of data:</italic> Jennifer L. Bragg-Gresham, Margaret DeAngelis, Lars G. Fritsche, Mathias Gorski, Wilmar Igl, Ivana K. Kim</p><p id="P87"><italic>Team 2: single variant analysis:</italic> Lars G. Fritsche (lead), Iris M. Heid (lead), Gonçalo R. Abecasis (lead), Wilmar Igl (lead), Jennifer L. Bragg-Gresham, Gabriëlle H. S. Buitendijk, Valentina Cipriani, Margaret DeAngelis, Mathias Gorski, Felix Grassmann, Michelle Grunin, Jonathan L. Haines, Robert P. Igo Jr., Sudha K. Iyengar, Caroline C. W. Klaver, Matthias Olden, Klaus Stark, Xiaowei Zhan</p><p id="P88"><italic>Team 3: pathway and rare variant burden analysis:</italic> Lars G. Fritsche (lead), Jessica N. Cooke Bailey (lead), Matthew Schu (lead), Gonçalo R. Abecasis, Milam A. Brantley Jr., Matthew Brooks, Gabriëlle H. S. Buitendijk, Monique D. Courtenay, Margaret DeAngelis, Eiko K. de Jong, Anneke I. den Hollander, Lindsay A. Farrer, Felix Grassmann, Jonathan L. Haines, Iris M. Heid, Joshua D. Hoffman, Wilmar Igl, Robert P. Igo Jr., Sudha K. Iyengar, Yingda Jiang, Margaux A. Morrison, Matthias Olden, Margaret A. Pericak-Vance, Rebecca J. Sardell, William K. Scott, Klaus Stark, Anand Swaroop, Bernhard H. F. Weber, Daniel E. Weeks, Xiaowei Zhan</p><p id="P89"><italic>Team 4: analysis of non-SNP variation:</italic> Robert P. Igo Jr. (lead), Sudha K. Iyengar (lead), Paul N. Baird (lead), Gonçalo R. Abecasis, Monique D. Courtenay, Lars G. Fritsche, Jonathan L. Haines</p><p id="P90"><italic>Team 5: functional data analysis:</italic> Dwight Stambolian (lead), Bernhard H. F. Weber (lead), Margaret DeAngelis (lead), Sudha K. Iyengar (lead), Valentina Cipriani, Jessica N. Cooke Bailey, Monique D. Courtenay, Eiko K. de Jong, Anneke I. den Hollander, Sascha Fauser, Lars G. Fritsche, Felix Grassmann, Jonathan L. Haines, Caroline Hayward, Iris M. Heid, Wilmar Igl, Denise J. Morgan, Margaux A. Morrison, Rinki Ratnapriya, Chloe M. Stanton, Anand Swaroop, Xiaowei Zhan</p></app><app id="APP4"><title>Design of Overall Experiment</title><p id="P91">Gonçalo R. Abecasis, Margaret DeAngelis, Lars G. Fritsche, Jonathan L. Haines, Iris M. Heid, Sudha K. Iyengar, Margaret A. Pericak-Vance, Bernhard H. F. Weber</p></app><app id="APP5"><title>Genotyping and QC</title><p id="P92">Kimberly F. Doheny (lead), Jane Romm (lead), Lars G. Fritsche (lead), Mathias Gorski (lead), Gonçalo R. Abecasis, Jennifer L. Bragg-Gresham, Monique D. Courtenay, Felix Grassmann, Jonathan L. Haines, Iris M. Heid, Joshua D. Hoffman, Wilmar Igl, Matthias Olden, Xiaowei Zhan</p></app><app id="APP6"><title>Writing Team</title><p id="P93">Lars G. Fritsche (lead), Iris M. Heid (lead), Gonçalo R. Abecasis, Jessica N. Cooke Bailey, Margaret DeAngelis, Jonathan L. Haines, Wilmar Igl, Sudha K. Iyengar, Ivana K. Kim, Dwight Stambolian, Bernhard H. F. Weber</p></app><app id="APP7"><title>Critical review of manuscript</title><p id="P94">Gonçalo R. Abecasis, Rando Allikmets, Paul N. Baird, Murray H. Brilliant, Itay Chowers, Jessica N. Cooke Bailey, Margaret DeAngelis, Sascha Fauser, Anneke I. den Hollander, Lindsay A. Farrer, Lars G. Fritsche, Michael B. Gorin, Stephanie A. Hagstrom, Jonathan L. Haines, Caroline Hayward, Iris M. Heid, Alex W. Hewitt, Wilmar Igl, Sudha K. Iyengar, Ivana K. Kim, Caroline C. W. Klaver, Barbara E. K. Klein, Michael L. Klein, Ronald Klein, Thierry Léveillard, Andrew Lotery, Paul Mitchell, Anthony T. Moore, Kyu Hyung Park, Neal S. Peachey, Margaret A. Pericak-Vance, Debra A. Schaumberg, Dwight Stambolian, Anand Swaroop, Jie Jin Wang, Bernhard H. F. Weber, Daniel E. Weeks, John R. W. Yates, Kang Zhang</p></app><app id="APP8"><title>Steering Committee of IAMDGC consortium</title><p id="P95">Anand Swaroop, Gonçalo R. Abecasis, Alex W. Hewitt, Murray H. Brilliant, Kang Zhang, Bernhard H. F. Weber, Iris M. Heid, Margaret DeAngelis, Lindsay A. Farrer, Kyu Hyung Park, Ivana K. Kim, Dwight Stambolian, Thierry Léveillard, Andrew Lotery, Itay Chowers, Sudha K. Iyengar, Stephanie A. Hagstrom, Neal S. Peachey, Barbara E. K. Klein, Ronald Klein, Debra A. Schaumberg, Margaret A. Pericak-Vance, Paul Mitchell, Jie Jin Wang, Rando Allikmets, Anthony T. Moore, John R. W. Yates, Jonathan L. Haines, Sascha Fauser, Anneke I. den Hollander, Paul N. Baird, Michael L. Klein, Michael B. Gorin, Daniel E. Weeks, Caroline Hayward, Caroline C. W. Klaver</p></app><app id="APP9"><title>Senior Executive Committee of IAMDGC consortium</title><p id="P96">Gonçalo R. Abecasis, Margaret DeAngelis, Jonathan L. Haines, Sudha K. Iyengar, Margaret A. Pericak-Vance, Bernhard H. F. Weber</p></app><app id="APP10"><title>Accession Code</title><p id="P97">Data permitted for sharing by respective Institutional Review Boards, and/summary statistics reported in the paper will be archived in the database of Genotypes and Phenotypes (dbGaP) under accession phs001039.v1.p1. Full GWAS summary statistics are available at <ext-link ext-link-type="uri" xlink:href="http://amdgenetics.org/">http://amdgenetics.org/</ext-link>.</p></app><app id="APP11"><title>Conflicts of Interest</title><p id="P98">Inventor status for patents held by University of Pittsburgh regarding the 10q26 AMD susceptibility locus (DEW, MBG). VC, ATM and JRW are co-inventors or beneficiaries of patents related to genetic discoveries in AMD. IC serves as a consultant for Novartis, Bayer, Allergan, and Lycored. Royalties for AMD patents held by the University of Regensburg (LGF, BHFW), Royalties for AMD patents held by the University of Michigan (GRA, AS, MIO, KEB), Scientific Advisory Board for Regeneron Genetics Center (GRA). PM holds a consultant position for Bayer Inc. and Novartis Inc. AL has acted as a consultant to Bayer, Allergan, Roche and Novartis Pharmaceuticals. SGS has acted as a consultant to Alimera and Bausch + Lomb and has received writing fees from Vindico.</p></app></app-group></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Genome-wide search reveals 34 loci and genes with rare variant burden for AMD</title><p>(<bold>a</bold>) We conducted a genome-wide single variant association analysis for >12 million variants in 16,144 advanced AMD patients versus 17,832 controls. Shown is the Manhattan Plot exhibiting P-values for association highlighting novel (P < 5×10<sup>–8</sup> for the first time, green) and known (blue) AMD loci (see <xref rid="T1" ref-type="table">Table 1</xref>). (<bold>b</bold>) We computed independent effect size (Odds Ratios) of each of the 52 identified variants (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). Shown are these effect sizes versus the frequency of the AMD risk increasing allele and a 80% power curve. (<bold>c</bold>) We conducted a genome-wide gene-based test for disease burden based on the protein-altering variants testing 17,044 RefSeq genes by the variable threshold test<sup><xref rid="R51" ref-type="bibr">51</xref></sup>. Shown is the Manhattan Plot with P-values, the red horizontal line indicating genome-wide significance (P ≤ 0.05/17,044 = 2.9×10<sup>–6</sup>) and the yellow line indicating AMD-locus-wide significance (given 703 genes in the 34 AMD loci, P ≤ 0.05/703 = 7.1×10<sup>–5</sup>). No gene outside the 34 loci is genome-wide significant; 14 genes are AMD-locus-wide significant (blue), four remain significant after locus-wide conditioning (bold letters, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 11</xref>).</p></caption><graphic xlink:href="nihms733253f1"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Genes with top priority based on biological and statistical evidence combined</title><p>We queried 368 genes in the 34 narrow AMD regions (index and proxies, r<sup><xref rid="R2" ref-type="bibr">2</xref></sup> ≥0.5, ±100kb) for biological (red; expression in retina/RPE/choroid, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 6</xref>; ocular mouse phenotype, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 7</xref>), statistical, (blue; ≥1 credible set variant in gene ±50 kb, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 3</xref>; rare variant burden, <xref rid="T2" ref-type="table">Table 2</xref>), putative functional (green; ≥ 1 credible set variant in gene ±50 kb being protein-altering, 5′/3′ UTR, other exonic, or putative promoter, <xref rid="SD1" ref-type="supplementary-material">Supplementary File 3</xref>), and molecular (magenta; enriched molecular pathway, drug target) evidence. We here focus on the gene(s) with the highest gene priority score (GPS) per locus (full list of genes in <xref rid="SD1" ref-type="supplementary-material">Supplementary File 9</xref>). Shown are <bold>(a)</bold> the 16 genes with highest GPS in the 15 novel AMD loci (one novel locus without any gene), and (<bold>b)</bold> the 25 genes with highest GPS in the 18 known AMD loci. Colored fields indicate yes and GPS counts number of colored fields per row.</p></caption><graphic xlink:href="nihms733253f2"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><title>Comparison of advanced AMD subtypes and intermediate versus advanced AMD</title><p>We compared associations of the 34 lead variants across different AMD phenotypes. Shown are effect sizes (log Odds Ratio) per minor allele in controls as well as 95% confidence intervals (widths and heights of diamonds). <bold>(a</bold>) Comparison of neovascular disease (10,749 CNV cases vs. 17,832 controls) and GA (3,235 GA cases vs. 17,832 controls) identified four variants (in loci <italic>MMP9</italic>, <italic>ARMS2</italic>/<italic>HTRA1</italic>, <italic>CETP</italic>, and <italic>SYN3</italic>/<italic>TIMP3</italic>) with significantly different association comparing CNV with GA (P<sub>diff</sub> < 0.05/34, marked in red, see also <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 16</xref>). (<bold>b)</bold> Comparison of intermediate AMD (6,657 cases vs. 17,832 controls) with advanced AMD (16,144 cases vs. 17,832 controls) identifies 24 variants with nominally significant (P < 0.05, marked in red) association with intermediate AMD (P<sub>binomial</sub> = 4.8 × 10<sup>–24</sup>), all of which have the same effect direction and less extreme effect sizes compared to advanced AMD (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 17</xref>).</p></caption><graphic xlink:href="nihms733253f3"></graphic></fig><fig id="F4" orientation="portrait" position="float"><label>Figure 4</label><caption><title>Variance explained and absolute risk of disease based on the 52 identified variants</title><p>(<bold>a</bold>) Absolute disease risk (=proportion of affected) by genetic risk score intervals (deciles and top 10 percentiles in embedded bar plot) based on our cases-control-data weighted to model a general population with 5% disease prevalence (see also <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 20</xref>). (<bold>b</bold>) Shown is disease liability explained by the 52 identified variants (bars) compared to the genomic heritability based on all genotyped variants (red lines) assuming disease prevalence of 1%, 5%, or 10%, respectively.</p></caption><graphic xlink:href="nihms733253f4"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><title>Thirty-four loci for age-related macular degeneration</title><p>Our genome-wide single-variant association analysis identified 34 loci for advanced AMD with genome-wide significance (P < 5 × 10<sup>–8</sup>) based on logistic regression in 16,144 cases and 17,832 controls of European ancestry. Shown are P-values and effect sizes (Odds Ratios, OR) for the variant with the smallest P-value per locus (lead variant) and the number of independent signals per locus (see <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>)</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" rowspan="3" align="left" colspan="1">Lead Variant</th><th valign="middle" rowspan="3" align="right" colspan="1">Chr</th><th valign="middle" rowspan="3" align="right" colspan="1">Position<xref rid="TFN2" ref-type="table-fn">a</xref></th><th valign="middle" rowspan="3" align="center" colspan="1">Major/minor allele</th><th valign="middle" rowspan="3" align="left" colspan="1">Locus name<xref rid="TFN3" ref-type="table-fn">b</xref></th><th valign="middle" rowspan="3" align="center" colspan="1"># Signals<xref rid="TFN4" ref-type="table-fn">c</xref></th><th colspan="3" valign="middle" align="center" rowspan="1">MAF</th><th colspan="3" valign="middle" align="center" rowspan="1">Association</th></tr><tr><th valign="bottom" colspan="4" rowspan="1"><hr></hr></th></tr><tr><th valign="middle" align="center" rowspan="1" colspan="1">Cases</th><th valign="middle" align="center" rowspan="1" colspan="1">Controls</th><th valign="middle" align="center" rowspan="1" colspan="1">OR</th><th valign="middle" align="center" rowspan="1" colspan="1"><italic>P</italic></th></tr></thead><tbody><tr><td colspan="10" valign="top" align="left" rowspan="1">KNOWN (previously reported with genome-wide significance, P < 5 × 10<sup>–8</sup>)</td></tr><tr><td colspan="10" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs10922109</td><td valign="middle" align="right" rowspan="1" colspan="1">1</td><td valign="middle" align="right" rowspan="1" colspan="1">196,704,632</td><td valign="middle" align="center" rowspan="1" colspan="1">C/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CFH</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">8</td><td valign="middle" align="center" rowspan="1" colspan="1">0.223</td><td valign="middle" align="center" rowspan="1" colspan="1">0.426</td><td valign="middle" align="center" rowspan="1" colspan="1">0.38</td><td valign="middle" align="center" rowspan="1" colspan="1">9.6 × 10<sup>–618</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs62247658</td><td valign="middle" align="right" rowspan="1" colspan="1">3</td><td valign="middle" align="right" rowspan="1" colspan="1">64,715,155</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>ADAMTS9-AS2</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.466</td><td valign="middle" align="center" rowspan="1" colspan="1">0.433</td><td valign="middle" align="center" rowspan="1" colspan="1">1.14</td><td valign="middle" align="center" rowspan="1" colspan="1">1.8 × 10<sup>–14</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs140647181</td><td valign="middle" align="right" rowspan="1" colspan="1">3</td><td valign="middle" align="right" rowspan="1" colspan="1">99,180,668</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>COL8A1</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.023</td><td valign="middle" align="center" rowspan="1" colspan="1">0.016</td><td valign="middle" align="center" rowspan="1" colspan="1">1.59</td><td valign="middle" align="center" rowspan="1" colspan="1">1.4 × 10<sup>–11</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs10033900</td><td valign="middle" align="right" rowspan="1" colspan="1">4</td><td valign="middle" align="right" rowspan="1" colspan="1">110,659,067</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CFI</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.511</td><td valign="middle" align="center" rowspan="1" colspan="1">0.477</td><td valign="middle" align="center" rowspan="1" colspan="1">1.15</td><td valign="middle" align="center" rowspan="1" colspan="1">5.4 × 10<sup>–17</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs62358361</td><td valign="middle" align="right" rowspan="1" colspan="1">5</td><td valign="middle" align="right" rowspan="1" colspan="1">39,327,888</td><td valign="middle" align="center" rowspan="1" colspan="1">G/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>C9</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.016</td><td valign="middle" align="center" rowspan="1" colspan="1">0.009</td><td valign="middle" align="center" rowspan="1" colspan="1">1.80</td><td valign="middle" align="center" rowspan="1" colspan="1">1.3 × 10<sup>–14</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs116503776</td><td valign="middle" align="right" rowspan="1" colspan="1">6</td><td valign="middle" align="right" rowspan="1" colspan="1">31,930,462</td><td valign="middle" align="center" rowspan="1" colspan="1">G/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>C2/CFB/SKIV2L</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">4</td><td valign="middle" align="center" rowspan="1" colspan="1">0.090</td><td valign="middle" align="center" rowspan="1" colspan="1">0.148</td><td valign="middle" align="center" rowspan="1" colspan="1">0.57</td><td valign="middle" align="center" rowspan="1" colspan="1">1.2 × 10<sup>–103</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs943080</td><td valign="middle" align="right" rowspan="1" colspan="1">6</td><td valign="middle" align="right" rowspan="1" colspan="1">43,826,627</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>VEGFA</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.465</td><td valign="middle" align="center" rowspan="1" colspan="1">0.497</td><td valign="middle" align="center" rowspan="1" colspan="1">0.88</td><td valign="middle" align="center" rowspan="1" colspan="1">1.1 × 10<sup>–14</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs79037040</td><td valign="middle" align="right" rowspan="1" colspan="1">8</td><td valign="middle" align="right" rowspan="1" colspan="1">23,082,971</td><td valign="middle" align="center" rowspan="1" colspan="1">T/G</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>TNFRSF10A</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.451</td><td valign="middle" align="center" rowspan="1" colspan="1">0.479</td><td valign="middle" align="center" rowspan="1" colspan="1">0.90</td><td valign="middle" align="center" rowspan="1" colspan="1">4.5 × 10<sup>–11</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs1626340</td><td valign="middle" align="right" rowspan="1" colspan="1">9</td><td valign="middle" align="right" rowspan="1" colspan="1">101,923,372</td><td valign="middle" align="center" rowspan="1" colspan="1">G/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>TGFBR1</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.189</td><td valign="middle" align="center" rowspan="1" colspan="1">0.209</td><td valign="middle" align="center" rowspan="1" colspan="1">0.88</td><td valign="middle" align="center" rowspan="1" colspan="1">3.8 × 10<sup>–10</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs3750846</td><td valign="middle" align="right" rowspan="1" colspan="1">10</td><td valign="middle" align="right" rowspan="1" colspan="1">124,215,565</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>ARMS2/HTRA1</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.436</td><td valign="middle" align="center" rowspan="1" colspan="1">0.208</td><td valign="middle" align="center" rowspan="1" colspan="1">2.81</td><td valign="middle" align="center" rowspan="1" colspan="1">6.5 × 10<sup>–735</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs9564692</td><td valign="middle" align="right" rowspan="1" colspan="1">13</td><td valign="middle" align="right" rowspan="1" colspan="1">31,821,240</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>B3GALTL</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.277</td><td valign="middle" align="center" rowspan="1" colspan="1">0.299</td><td valign="middle" align="center" rowspan="1" colspan="1">0.89</td><td valign="middle" align="center" rowspan="1" colspan="1">3.3 × 10<sup>–10</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs61985136</td><td valign="middle" align="right" rowspan="1" colspan="1">14</td><td valign="middle" align="right" rowspan="1" colspan="1">68,769,199</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>RAD51B</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.360</td><td valign="middle" align="center" rowspan="1" colspan="1">0.384</td><td valign="middle" align="center" rowspan="1" colspan="1">0.90</td><td valign="middle" align="center" rowspan="1" colspan="1">1.6 × 10<sup>–10</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs2043085</td><td valign="middle" align="right" rowspan="1" colspan="1">15</td><td valign="middle" align="right" rowspan="1" colspan="1">58,680,954</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>LIPC</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.350</td><td valign="middle" align="center" rowspan="1" colspan="1">0.381</td><td valign="middle" align="center" rowspan="1" colspan="1">0.87</td><td valign="middle" align="center" rowspan="1" colspan="1">4.3 × 10<sup>–15</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs5817082</td><td valign="middle" align="right" rowspan="1" colspan="1">16</td><td valign="middle" align="right" rowspan="1" colspan="1">56,997,349</td><td valign="middle" align="center" rowspan="1" colspan="1">C/CA</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CETP</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.232</td><td valign="middle" align="center" rowspan="1" colspan="1">0.264</td><td valign="middle" align="center" rowspan="1" colspan="1">0.84</td><td valign="middle" align="center" rowspan="1" colspan="1">3.6 × 10<sup>–19</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs2230199</td><td valign="middle" align="right" rowspan="1" colspan="1">19</td><td valign="middle" align="right" rowspan="1" colspan="1">6,718,387</td><td valign="middle" align="center" rowspan="1" colspan="1">C/G</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>C3</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">3</td><td valign="middle" align="center" rowspan="1" colspan="1">0.266</td><td valign="middle" align="center" rowspan="1" colspan="1">0.208</td><td valign="middle" align="center" rowspan="1" colspan="1">1.43</td><td valign="middle" align="center" rowspan="1" colspan="1">3.8 × 10<sup>–69</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs429358</td><td valign="middle" align="right" rowspan="1" colspan="1">19</td><td valign="middle" align="right" rowspan="1" colspan="1">45,411,941</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>APOE</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">2</td><td valign="middle" align="center" rowspan="1" colspan="1">0.099</td><td valign="middle" align="center" rowspan="1" colspan="1">0.135</td><td valign="middle" align="center" rowspan="1" colspan="1">0.70</td><td valign="middle" align="center" rowspan="1" colspan="1">2.4 × 10<sup>–42</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs5754227</td><td valign="middle" align="right" rowspan="1" colspan="1">22</td><td valign="middle" align="right" rowspan="1" colspan="1">33,105,817</td><td valign="middle" align="center" rowspan="1" colspan="1">T/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>SYN3/TIMP3</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.109</td><td valign="middle" align="center" rowspan="1" colspan="1">0.137</td><td valign="middle" align="center" rowspan="1" colspan="1">0.77</td><td valign="middle" align="center" rowspan="1" colspan="1">1.1 × 10<sup>–24</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs8135665</td><td valign="middle" align="right" rowspan="1" colspan="1">22</td><td valign="middle" align="right" rowspan="1" colspan="1">38,476,276</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>SLC16A8</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.217</td><td valign="middle" align="center" rowspan="1" colspan="1">0.195</td><td valign="middle" align="center" rowspan="1" colspan="1">1.14</td><td valign="middle" align="center" rowspan="1" colspan="1">5.5 × 10<sup>–11</sup></td></tr><tr><td colspan="10" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td colspan="10" valign="top" align="left" rowspan="1">NOVEL (reported with genome-wide significance, P < 5 × 10<sup>–8</sup>, for the first time)</td></tr><tr><td colspan="10" valign="bottom" rowspan="1"><hr></hr></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs11884770</td><td valign="middle" align="right" rowspan="1" colspan="1">2</td><td valign="middle" align="right" rowspan="1" colspan="1">228,086,920</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>COL4A3</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.258</td><td valign="middle" align="center" rowspan="1" colspan="1">0.278</td><td valign="middle" align="center" rowspan="1" colspan="1">0.90</td><td valign="middle" align="center" rowspan="1" colspan="1">2.9 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs114092250</td><td valign="middle" align="right" rowspan="1" colspan="1">5</td><td valign="middle" align="right" rowspan="1" colspan="1">35,494,448</td><td valign="middle" align="center" rowspan="1" colspan="1">G/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>PRLR/SPEF2</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.016</td><td valign="middle" align="center" rowspan="1" colspan="1">0.022</td><td valign="middle" align="center" rowspan="1" colspan="1">0.70</td><td valign="middle" align="center" rowspan="1" colspan="1">2.1 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs7803454</td><td valign="middle" align="right" rowspan="1" colspan="1">7</td><td valign="middle" align="right" rowspan="1" colspan="1">99,991,548</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>PILRB/PILRA</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.209</td><td valign="middle" align="center" rowspan="1" colspan="1">0.190</td><td valign="middle" align="center" rowspan="1" colspan="1">1.13</td><td valign="middle" align="center" rowspan="1" colspan="1">4.8 × 10<sup>–9</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs1142</td><td valign="middle" align="right" rowspan="1" colspan="1">7</td><td valign="middle" align="right" rowspan="1" colspan="1">104,756,326</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>KMT2E/SRPK2</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.370</td><td valign="middle" align="center" rowspan="1" colspan="1">0.346</td><td valign="middle" align="center" rowspan="1" colspan="1">1.11</td><td valign="middle" align="center" rowspan="1" colspan="1">1.4 × 10<sup>–9</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs71507014</td><td valign="middle" align="right" rowspan="1" colspan="1">9</td><td valign="middle" align="right" rowspan="1" colspan="1">73,438,605</td><td valign="middle" align="center" rowspan="1" colspan="1">GC/G</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>TRPM3</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.427</td><td valign="middle" align="center" rowspan="1" colspan="1">0.405</td><td valign="middle" align="center" rowspan="1" colspan="1">1.10</td><td valign="middle" align="center" rowspan="1" colspan="1">3.0 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs10781182</td><td valign="middle" align="right" rowspan="1" colspan="1">9</td><td valign="middle" align="right" rowspan="1" colspan="1">76,617,720</td><td valign="middle" align="center" rowspan="1" colspan="1">G/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>MIR6130/RORB</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.328</td><td valign="middle" align="center" rowspan="1" colspan="1">0.306</td><td valign="middle" align="center" rowspan="1" colspan="1">1.11</td><td valign="middle" align="center" rowspan="1" colspan="1">2.6 × 10<sup>–9</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs2740488</td><td valign="middle" align="right" rowspan="1" colspan="1">9</td><td valign="middle" align="right" rowspan="1" colspan="1">107,661,742</td><td valign="middle" align="center" rowspan="1" colspan="1">A/C</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>ABCA1</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.255</td><td valign="middle" align="center" rowspan="1" colspan="1">0.275</td><td valign="middle" align="center" rowspan="1" colspan="1">0.90</td><td valign="middle" align="center" rowspan="1" colspan="1">1.2 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs12357257</td><td valign="middle" align="right" rowspan="1" colspan="1">10</td><td valign="middle" align="right" rowspan="1" colspan="1">24,999,593</td><td valign="middle" align="center" rowspan="1" colspan="1">G/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>ARHGAP21</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.243</td><td valign="middle" align="center" rowspan="1" colspan="1">0.223</td><td valign="middle" align="center" rowspan="1" colspan="1">1.11</td><td valign="middle" align="center" rowspan="1" colspan="1">4.4 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs3138141</td><td valign="middle" align="right" rowspan="1" colspan="1">12</td><td valign="middle" align="right" rowspan="1" colspan="1">56,115,778</td><td valign="middle" align="center" rowspan="1" colspan="1">C/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>RDH5/CD63</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.222</td><td valign="middle" align="center" rowspan="1" colspan="1">0.207</td><td valign="middle" align="center" rowspan="1" colspan="1">1.16</td><td valign="middle" align="center" rowspan="1" colspan="1">4.3 × 10<sup>–9</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs61941274</td><td valign="middle" align="right" rowspan="1" colspan="1">12</td><td valign="middle" align="right" rowspan="1" colspan="1">112,132,610</td><td valign="middle" align="center" rowspan="1" colspan="1">G/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>ACAD10</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.024</td><td valign="middle" align="center" rowspan="1" colspan="1">0.018</td><td valign="middle" align="center" rowspan="1" colspan="1">1.51</td><td valign="middle" align="center" rowspan="1" colspan="1">1.1 × 10<sup>–9</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs72802342</td><td valign="middle" align="right" rowspan="1" colspan="1">16</td><td valign="middle" align="right" rowspan="1" colspan="1">75,234,872</td><td valign="middle" align="center" rowspan="1" colspan="1">C/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CTRB2/CTRB1</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.067</td><td valign="middle" align="center" rowspan="1" colspan="1">0.080</td><td valign="middle" align="center" rowspan="1" colspan="1">0.79</td><td valign="middle" align="center" rowspan="1" colspan="1">5.0 × 10<sup>–12</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs11080055</td><td valign="middle" align="right" rowspan="1" colspan="1">17</td><td valign="middle" align="right" rowspan="1" colspan="1">26,649,724</td><td valign="middle" align="center" rowspan="1" colspan="1">C/A</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>TMEM97/VTN</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.463</td><td valign="middle" align="center" rowspan="1" colspan="1">0.486</td><td valign="middle" align="center" rowspan="1" colspan="1">0.91</td><td valign="middle" align="center" rowspan="1" colspan="1">1.0 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs6565597</td><td valign="middle" align="right" rowspan="1" colspan="1">17</td><td valign="middle" align="right" rowspan="1" colspan="1">79,526,821</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>NPLOC4/TSPAN10</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.400</td><td valign="middle" align="center" rowspan="1" colspan="1">0.381</td><td valign="middle" align="center" rowspan="1" colspan="1">1.13</td><td valign="middle" align="center" rowspan="1" colspan="1">1.5 × 10<sup>–11</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs67538026</td><td valign="middle" align="right" rowspan="1" colspan="1">19</td><td valign="middle" align="right" rowspan="1" colspan="1">1,031,438</td><td valign="middle" align="center" rowspan="1" colspan="1">C/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CNN2</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.460</td><td valign="middle" align="center" rowspan="1" colspan="1">0.498</td><td valign="middle" align="center" rowspan="1" colspan="1">0.90</td><td valign="middle" align="center" rowspan="1" colspan="1">2.6 × 10<sup>–8</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs142450006</td><td valign="middle" align="right" rowspan="1" colspan="1">20</td><td valign="middle" align="right" rowspan="1" colspan="1">44,614,991</td><td valign="middle" align="center" rowspan="1" colspan="1">TTTTC/T</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>MMP9</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.124</td><td valign="middle" align="center" rowspan="1" colspan="1">0.141</td><td valign="middle" align="center" rowspan="1" colspan="1">0.85</td><td valign="middle" align="center" rowspan="1" colspan="1">2.4 × 10<sup>–10</sup></td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1">rs201459901</td><td valign="middle" align="right" rowspan="1" colspan="1">20</td><td valign="middle" align="right" rowspan="1" colspan="1">56,653,724</td><td valign="middle" align="center" rowspan="1" colspan="1">T/TA</td><td valign="middle" align="left" rowspan="1" colspan="1"><italic>C20orf85</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">1</td><td valign="middle" align="center" rowspan="1" colspan="1">0.054</td><td valign="middle" align="center" rowspan="1" colspan="1">0.070</td><td valign="middle" align="center" rowspan="1" colspan="1">0.76</td><td valign="middle" align="center" rowspan="1" colspan="1">3.1 × 10<sup>–16</sup></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>Chr = Chromosome; MAF = minor allele frequency; OR = Odds Ratio</p></fn><fn id="TFN2"><label>a</label><p>Chromosomal position is given based on NCBI RefSeq hg19;</p></fn><fn id="TFN3"><label>b</label><p>The locus name is a label of the region using the nearest gene(s), but does not necessarily state the responsible gene;</p></fn><fn id="TFN4"><label>c</label><p>number of independent variants in this locus; hg19 = human genome reference assembly (version 19)</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><title>Four genes with a significant rare variant burden within the 34 AMD loci independent from other identified variants</title><p>We computed a gene-based burden test of rare protein-altering variants comparing 16,144 advanced AMD cases and 17,832 controls. Shown are P-values from the variable threshold test (up to 100 million permutations) and Odds Ratios from the collapsed burden test, both adjusted for the other identified variants in the respective locus (locus-wide conditioning). Four genes (among the 703 genes in the 34 AMD locus regions) showed a significant (P < 0.05/703 = 7.1 × 10<sup>–5</sup>) burden. Details about the corresponding rare variants underlying the observed burden can be found in <xref rid="SD1" ref-type="supplementary-material">Supplementary File 4</xref>. Results for the 14 genes that show significant burden within the 34 AMD loci without locus-wide conditioning are shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 11</xref>. Rare variants were defined here as variants with minor allele frequency in cases and controls < 1% in each of the ancestries, European, Asian, and African.</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="middle" rowspan="3" align="left" colspan="1">Gene</th><th valign="middle" rowspan="3" align="center" colspan="1">Optimal Threshold for Rare Variants Count (%)</th><th valign="middle" align="center" rowspan="1" colspan="1">Number of Variants below Optimal RAC</th><th colspan="2" valign="middle" align="center" rowspan="1">Summed Rare Allele Count (Frequency [%])</th><th valign="middle" rowspan="3" align="center" colspan="1"><italic>P</italic><xref rid="TFN6" ref-type="table-fn">a</xref></th><th valign="middle" rowspan="3" align="center" colspan="1">Odds Ratio</th></tr><tr><th valign="bottom" colspan="3" rowspan="1"><hr></hr></th></tr><tr><th valign="middle" align="center" rowspan="1" colspan="1">Total (Exome Chip Base + Custom)</th><th valign="middle" align="center" rowspan="1" colspan="1">Cases N = 16,144</th><th valign="middle" align="center" rowspan="1" colspan="1">Controls N = 17,832</th></tr></thead><tbody><tr><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CFH</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">10 (0.015%)</td><td valign="middle" align="center" rowspan="1" colspan="1">37 (9+28)</td><td valign="middle" align="center" rowspan="1" colspan="1">88 (0.273%)</td><td valign="middle" align="center" rowspan="1" colspan="1">38 (0.107%)</td><td valign="middle" align="center" rowspan="1" colspan="1">1.2 × 10<sup>–6</sup></td><td valign="middle" align="center" rowspan="1" colspan="1">2.94</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"><italic>CFI</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">46 (0.068%)</td><td valign="middle" align="center" rowspan="1" colspan="1">43 (17+26)</td><td valign="middle" align="center" rowspan="1" colspan="1">213 (0.660%)</td><td valign="middle" align="center" rowspan="1" colspan="1">82 (0.230%)</td><td valign="middle" align="center" rowspan="1" colspan="1">1.0 × 10<sup>–8</sup></td><td valign="middle" align="center" rowspan="1" colspan="1">2.95</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"><italic>TIMP3</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">14 (0.021%)</td><td valign="middle" align="center" rowspan="1" colspan="1">9 (1+8)</td><td valign="middle" align="center" rowspan="1" colspan="1">29 (0.0898%)</td><td valign="middle" align="center" rowspan="1" colspan="1">1 (0.00280%)</td><td valign="middle" align="center" rowspan="1" colspan="1">9.0 × 10<sup>–8</sup></td><td valign="middle" align="center" rowspan="1" colspan="1">31.21</td></tr><tr><td valign="middle" align="left" rowspan="1" colspan="1"><italic>SLC16A8</italic></td><td valign="middle" align="center" rowspan="1" colspan="1">648 (0.954%)</td><td valign="middle" align="center" rowspan="1" colspan="1">9 (7+2)</td><td valign="middle" align="center" rowspan="1" colspan="1">487 (1.51%)</td><td valign="middle" align="center" rowspan="1" colspan="1">392 (1.10%)</td><td valign="middle" align="center" rowspan="1" colspan="1">3.1 × 10<sup>–6</sup></td><td valign="middle" align="center" rowspan="1" colspan="1">1.40</td></tr></tbody></table><table-wrap-foot><fn id="TFN5"><p>RAC = rare allele count;</p></fn><fn id="TFN6"><label>a</label><p>P-values are from the variable threshold test conditioned on other identified variants in the locus (locus-wide conditioned).</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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