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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Meta-analyses identify 13 novel loci associated with age at menopause and highlights DNA repair and immune pathways</title><author><name sortKey="Stolk, Lisette" sort="Stolk, Lisette" uniqKey="Stolk L" first="Lisette" last="Stolk">Lisette Stolk</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Perry, John Rb" sort="Perry, John Rb" uniqKey="Perry J" first="John Rb" last="Perry">John Rb Perry</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="He, Chunyan" sort="He, Chunyan" uniqKey="He C" first="Chunyan" last="He">Chunyan He</name><affiliation><nlm:aff id="A7">Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA</nlm:aff></affiliation></author><author><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Sulem, Patrick" sort="Sulem, Patrick" uniqKey="Sulem P" first="Patrick" last="Sulem">Patrick Sulem</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Barbalic, Maja" sort="Barbalic, Maja" uniqKey="Barbalic M" first="Maja" last="Barbalic">Maja Barbalic</name><affiliation><nlm:aff id="A11">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Byrne, Enda M" sort="Byrne, Enda M" uniqKey="Byrne E" first="Enda M" last="Byrne">Enda M. Byrne</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Ernst, Florian" sort="Ernst, Florian" uniqKey="Ernst F" first="Florian" last="Ernst">Florian Ernst</name><affiliation><nlm:aff id="A14">Interfakultäres Institut für Genomforschung, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Estonian Biocenter, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Franceschini, Nora" sort="Franceschini, Nora" uniqKey="Franceschini N" first="Nora" last="Franceschini">Nora Franceschini</name><affiliation><nlm:aff id="A18">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Gudbjartsson, Daniel F" sort="Gudbjartsson, Daniel F" uniqKey="Gudbjartsson D" first="Daniel F" last="Gudbjartsson">Daniel F. Gudbjartsson</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Hottenga, Jouke Jan" sort="Hottenga, Jouke Jan" uniqKey="Hottenga J" first="Jouke-Jan" last="Hottenga">Jouke-Jan Hottenga</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Broad Institute of Harvard and MIT, USA</nlm:aff></affiliation></author><author><name sortKey="Mcardle, Patick F" sort="Mcardle, Patick F" uniqKey="Mcardle P" first="Patick F" last="Mcardle">Patick F. Mcardle</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Porcu, Eleonora" sort="Porcu, Eleonora" uniqKey="Porcu E" first="Eleonora" last="Porcu">Eleonora Porcu</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V" last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Van Wingerden, Sophie" sort="Van Wingerden, Sophie" uniqKey="Van Wingerden S" first="Sophie" last="Van Wingerden">Sophie Van Wingerden</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhai, Guangju" sort="Zhai, Guangju" uniqKey="Zhai G" first="Guangju" last="Zhai">Guangju Zhai</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada</nlm:aff></affiliation></author><author><name sortKey="Zhuang, Wei V" sort="Zhuang, Wei V" uniqKey="Zhuang W" first="Wei V" last="Zhuang">Wei V. Zhuang</name><affiliation><nlm:aff id="A28">Department of Biostatistics, Boston University School of Public Health, Boston Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Eva" sort="Albrecht, Eva" uniqKey="Albrecht E" first="Eva" last="Albrecht">Eva Albrecht</name><affiliation><nlm:aff id="A29">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Alizadeh, Behrooz Z" sort="Alizadeh, Behrooz Z" uniqKey="Alizadeh B" first="Behrooz Z" last="Alizadeh">Behrooz Z. Alizadeh</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Bandinelli, Stefania" sort="Bandinelli, Stefania" uniqKey="Bandinelli S" first="Stefania" last="Bandinelli">Stefania Bandinelli</name><affiliation><nlm:aff id="A31">Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy</nlm:aff></affiliation></author><author><name sortKey="Lauc, Lovorka Barac" sort="Lauc, Lovorka Barac" uniqKey="Lauc L" first="Lovorka Barac" last="Lauc">Lovorka Barac Lauc</name><affiliation><nlm:aff id="A32">Croation Science Foundation, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Jacques S" sort="Beckmann, Jacques S" uniqKey="Beckmann J" first="Jacques S" last="Beckmann">Jacques S. Beckmann</name><affiliation><nlm:aff id="A33">Department of Medical Genetics, University of Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Boban, Mladen" sort="Boban, Mladen" uniqKey="Boban M" first="Mladen" last="Boban">Mladen Boban</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A11">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Broekmans, Frank J" sort="Broekmans, Frank J" uniqKey="Broekmans F" first="Frank J" last="Broekmans">Frank J. Broekmans</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Burri, Andrea" sort="Burri, Andrea" uniqKey="Burri A" first="Andrea" last="Burri">Andrea Burri</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J" last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="A38">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Chen, Constance" sort="Chen, Constance" uniqKey="Chen C" first="Constance" last="Chen">Constance Chen</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Corre, Tanguy" sort="Corre, Tanguy" uniqKey="Corre T" first="Tanguy" last="Corre">Tanguy Corre</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Coviello, Andrea D" sort="Coviello, Andrea D" uniqKey="Coviello A" first="Andrea D" last="Coviello">Andrea D. Coviello</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="D Damo, Pio" sort="D Damo, Pio" uniqKey="D Damo P" first="Pio" last="D Damo">Pio D Damo</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A44">University of Trieste, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Davies, Gail" sort="Davies, Gail" uniqKey="Davies G" first="Gail" last="Davies">Gail Davies</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="De Faire, Ulf" sort="De Faire, Ulf" uniqKey="De Faire U" first="Ulf" last="De Faire">Ulf De Faire</name><affiliation><nlm:aff id="A46">Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="De Geus, Eco Jc" sort="De Geus, Eco Jc" uniqKey="De Geus E" first="Eco Jc" last="De Geus">Eco Jc De Geus</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">EMGO+ Institute, VU Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Dedoussis, George Vz" sort="Dedoussis, George Vz" uniqKey="Dedoussis G" first="George Vz" last="Dedoussis">George Vz Dedoussis</name><affiliation><nlm:aff id="A49">Department of Nutrition and Dietetics, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Deloukas, Panagiotis" sort="Deloukas, Panagiotis" uniqKey="Deloukas P" first="Panagiotis" last="Deloukas">Panagiotis Deloukas</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Ebrahim, Shah" sort="Ebrahim, Shah" uniqKey="Ebrahim S" first="Shah" last="Ebrahim">Shah Ebrahim</name><affiliation><nlm:aff id="A50">Department of Epidemiology & Population Healths, London School of Hygiene & Tropical Medicine, UK</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Emilsson, Valur" sort="Emilsson, Valur" uniqKey="Emilsson V" first="Valur" last="Emilsson">Valur Emilsson</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A51">National Institute for Health and Welfare, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of General Practice and Primary Health Care, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A54">Folkhalsan Research Centre, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Vasa Central Hospital, Vasa, Finland</nlm:aff></affiliation></author><author><name sortKey="Fauser, Bart Cjm" sort="Fauser, Bart Cjm" uniqKey="Fauser B" first="Bart Cjm" last="Fauser">Bart Cjm Fauser</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ferreli, Liana" sort="Ferreli, Liana" uniqKey="Ferreli L" first="Liana" last="Ferreli">Liana Ferreli</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Ferrucci, Luigi" sort="Ferrucci, Luigi" uniqKey="Ferrucci L" first="Luigi" last="Ferrucci">Luigi Ferrucci</name><affiliation><nlm:aff id="A56">Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Fischer, Krista" sort="Fischer, Krista" uniqKey="Fischer K" first="Krista" last="Fischer">Krista Fischer</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Folsom, Aaron R" sort="Folsom, Aaron R" uniqKey="Folsom A" first="Aaron R" last="Folsom">Aaron R. Folsom</name><affiliation><nlm:aff id="A57">Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Garcia, Melissa E" sort="Garcia, Melissa E" uniqKey="Garcia M" first="Melissa E" last="Garcia">Melissa E. Garcia</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Gasparini, Paolo" sort="Gasparini, Paolo" uniqKey="Gasparini P" first="Paolo" last="Gasparini">Paolo Gasparini</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A44">University of Trieste, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="A29">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Glazer, Nicole" sort="Glazer, Nicole" uniqKey="Glazer N" first="Nicole" last="Glazer">Nicole Glazer</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation></author><author><name sortKey="Grobbee, Diederick E" sort="Grobbee, Diederick E" uniqKey="Grobbee D" first="Diederick E" last="Grobbee">Diederick E. Grobbee</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Haller, Toomas" sort="Haller, Toomas" uniqKey="Haller T" first="Toomas" last="Haller">Toomas Haller</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Hankinson, Susan E" sort="Hankinson, Susan E" uniqKey="Hankinson S" first="Susan E" last="Hankinson">Susan E. Hankinson</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hass, Merli" sort="Hass, Merli" uniqKey="Hass M" first="Merli" last="Hass">Merli Hass</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</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="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Heath, Andrew C" sort="Heath, Andrew C" uniqKey="Heath A" first="Andrew C" last="Heath">Andrew C. Heath</name><affiliation><nlm:aff id="A63">Washington University St.Louis, St. Louis, MO, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ingelsson, Erik" sort="Ingelsson, Erik" uniqKey="Ingelsson E" first="Erik" last="Ingelsson">Erik Ingelsson</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Janssens, A Cecile Jw" sort="Janssens, A Cecile Jw" uniqKey="Janssens A" first="A Cecile Jw" last="Janssens">A Cecile Jw Janssens</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D" last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kardia, Sharon Lr" sort="Kardia, Sharon Lr" uniqKey="Kardia S" first="Sharon Lr" last="Kardia">Sharon Lr Kardia</name><affiliation><nlm:aff id="A65">Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Keyzer, Jules" sort="Keyzer, Jules" uniqKey="Keyzer J" first="Jules" last="Keyzer">Jules Keyzer</name><affiliation><nlm:aff id="A66">Diagnostic GP laboratory Eindhoven, Eindhoven, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P" last="Kiel">Douglas P. Kiel</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kolcic, Ivana" sort="Kolcic, Ivana" uniqKey="Kolcic I" first="Ivana" last="Kolcic">Ivana Kolcic</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltán" last="Kutalik">Zoltán Kutalik</name><affiliation><nlm:aff id="A33">Department of Medical Genetics, University of Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Swiss Institute of Bioinformatics, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Lahti, Jari" sort="Lahti, Jari" uniqKey="Lahti J" first="Jari" last="Lahti">Jari Lahti</name><affiliation><nlm:aff id="A68">Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Lai, Sandra" sort="Lai, Sandra" uniqKey="Lai S" first="Sandra" last="Lai">Sandra Lai</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Laisk, Triin" sort="Laisk, Triin" uniqKey="Laisk T" first="Triin" last="Laisk">Triin Laisk</name><affiliation><nlm:aff id="A69">Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Laven, Joop Se" sort="Laven, Joop Se" uniqKey="Laven J" first="Joop Se" last="Laven">Joop Se Laven</name><affiliation><nlm:aff id="A70">Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lawlor, Debbie A" sort="Lawlor, Debbie A" uniqKey="Lawlor D" first="Debbie A" last="Lawlor">Debbie A. Lawlor</name><affiliation><nlm:aff id="A71">MRC Centre for Causal Analysis in Translational Epidemiology, School of Social & Community Medicine, University of Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="A72">Human genetic, Genome Institute of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M" last="Lopez">Lorna M. Lopez</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Louwers, Yvonne V" sort="Louwers, Yvonne V" uniqKey="Louwers Y" first="Yvonne V" last="Louwers">Yvonne V. Louwers</name><affiliation><nlm:aff id="A70">Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Magnusson, Patrik Ke" sort="Magnusson, Patrik Ke" uniqKey="Magnusson P" first="Patrik Ke" last="Magnusson">Patrik Ke Magnusson</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Marongiu, Mara" sort="Marongiu, Mara" uniqKey="Marongiu M" first="Mara" last="Marongiu">Mara Marongiu</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Klaric, Irena Martinovic" sort="Klaric, Irena Martinovic" uniqKey="Klaric I" first="Irena Martinovic" last="Klaric">Irena Martinovic Klaric</name><affiliation><nlm:aff id="A73">Institute for Migration and Ethnic Studies, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Masciullo, Corrado" sort="Masciullo, Corrado" uniqKey="Masciullo C" first="Corrado" last="Masciullo">Corrado Masciullo</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name><affiliation><nlm:aff id="A74">Department of Biostatistics, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Medland, Sarah E" sort="Medland, Sarah E" uniqKey="Medland S" first="Sarah E" last="Medland">Sarah E. Medland</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Melzer, David" sort="Melzer, David" uniqKey="Melzer D" first="David" last="Melzer">David Melzer</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Mooser, Vincent" sort="Mooser, Vincent" uniqKey="Mooser V" first="Vincent" last="Mooser">Vincent Mooser</name><affiliation><nlm:aff id="A75">Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, USA</nlm:aff></affiliation></author><author><name sortKey="Navarro, Pau" sort="Navarro, Pau" uniqKey="Navarro P" first="Pau" last="Navarro">Pau Navarro</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Newman, Anne B" sort="Newman, Anne B" uniqKey="Newman A" first="Anne B" last="Newman">Anne B. Newman</name><affiliation><nlm:aff id="A76">Departments of Epidemiology and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</nlm:aff></affiliation></author><author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Onland Moret, N Charlotte" sort="Onland Moret, N Charlotte" uniqKey="Onland Moret N" first="N. Charlotte" last="Onland-Moret">N. Charlotte Onland-Moret</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A77">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A78">Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Pare, Guillaume" sort="Pare, Guillaume" uniqKey="Pare G" first="Guillaume" last="Paré">Guillaume Paré</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A79">Genetic and Molecular Epidemiology Laboratory, McMaster University, Hamilton, ON Canada</nlm:aff></affiliation></author><author><name sortKey="Parker, Alex N" sort="Parker, Alex N" uniqKey="Parker A" first="Alex N" last="Parker">Alex N. Parker</name><affiliation><nlm:aff id="A80">Amgen, Cambridge, MA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A81">Foundation Medicine, Inc., Cambridge MA USA</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L" last="Pedersen">Nancy L. Pedersen</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Peeters, Petra Hm" sort="Peeters, Petra Hm" uniqKey="Peeters P" first="Petra Hm" last="Peeters">Petra Hm Peeters</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Pistis, Giorgio" sort="Pistis, Giorgio" uniqKey="Pistis G" first="Giorgio" last="Pistis">Giorgio Pistis</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Plump, Andrew S" sort="Plump, Andrew S" uniqKey="Plump A" first="Andrew S" last="Plump">Andrew S. Plump</name><affiliation><nlm:aff id="A83">Cardiovascular Disease, Merck Research Laboratory, Rahway, NJ, USA</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pop, Victor Jm" sort="Pop, Victor Jm" uniqKey="Pop V" first="Victor Jm" last="Pop">Victor Jm Pop</name><affiliation><nlm:aff id="A84">Department of Clinical Health Psychology, University of Tilburg, Tilburg, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A85">Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Group Health Research Institute, Group Health Cooperative, Seattle, WA USA</nlm:aff></affiliation></author><author><name sortKey="R Ikkonen, Katri" sort="R Ikkonen, Katri" uniqKey="R Ikkonen K" first="Katri" last="R Ikkönen">Katri R Ikkönen</name><affiliation><nlm:aff id="A68">Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Rehnberg, Emil" sort="Rehnberg, Emil" uniqKey="Rehnberg E" first="Emil" last="Rehnberg">Emil Rehnberg</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I" last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="A87">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Sala, Cinzia" sort="Sala, Cinzia" uniqKey="Sala C" first="Cinzia" last="Sala">Cinzia Sala</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Salumets, Andres" sort="Salumets, Andres" uniqKey="Salumets A" first="Andres" last="Salumets">Andres Salumets</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A69">Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Scuteri, Angelo" sort="Scuteri, Angelo" uniqKey="Scuteri A" first="Angelo" last="Scuteri">Angelo Scuteri</name><affiliation><nlm:aff id="A89">Lab Cardiovascular Sciences - NIA - NIH, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name><affiliation><nlm:aff id="A90">Laboratory of Neurogenetics, National Institute of Ageing, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A" last="Smith">Jennifer A. Smith</name><affiliation><nlm:aff id="A65">Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stacey, Simon N" sort="Stacey, Simon N" uniqKey="Stacey S" first="Simon N" last="Stacey">Simon N. Stacey</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Geriatric Medicine Unit, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Stathopoulou, Maria G" sort="Stathopoulou, Maria G" uniqKey="Stathopoulou M" first="Maria G" last="Stathopoulou">Maria G. Stathopoulou</name><affiliation><nlm:aff id="A49">Department of Nutrition and Dietetics, Harokopio University, Athens, Greece</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Cardiovascular Genetics Research Unit, EA4373, Université Henri Poincaré - Nancy 1, Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen" sort="Stirrups, Kathleen" uniqKey="Stirrups K" first="Kathleen" last="Stirrups">Kathleen Stirrups</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stolk, Ronald P" sort="Stolk, Ronald P" uniqKey="Stolk R" first="Ronald P" last="Stolk">Ronald P. Stolk</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Sun, Yan V" sort="Sun, Yan V" uniqKey="Sun Y" first="Yan V" last="Sun">Yan V. Sun</name><affiliation><nlm:aff id="A94">Department of Epidemiology, Emory University, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Tenesa, Albert" sort="Tenesa, Albert" uniqKey="Tenesa A" first="Albert" last="Tenesa">Albert Tenesa</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A95">The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK</nlm:aff></affiliation></author><author><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name><affiliation><nlm:aff id="A96">Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Toniolo, Daniela" sort="Toniolo, Daniela" uniqKey="Toniolo D" first="Daniela" last="Toniolo">Daniela Toniolo</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute of Molecular Genetics-CNR, Pavia, Italy</nlm:aff></affiliation></author><author><name sortKey="Tryggvadottir, Laufey" sort="Tryggvadottir, Laufey" uniqKey="Tryggvadottir L" first="Laufey" last="Tryggvadottir">Laufey Tryggvadottir</name><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Icelandic Cancer Registry, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Tsui, Kim" sort="Tsui, Kim" uniqKey="Tsui K" first="Kim" last="Tsui">Kim Tsui</name><affiliation><nlm:aff id="A80">Amgen, Cambridge, MA USA</nlm:aff></affiliation></author><author><name sortKey="Ulivi, Sheila" sort="Ulivi, Sheila" uniqKey="Ulivi S" first="Sheila" last="Ulivi">Sheila Ulivi</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Van Dam, Rob M" sort="Van Dam, Rob M" uniqKey="Van Dam R" first="Rob M" last="Van Dam">Rob M. Van Dam</name><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Van Der Schouw, Yvonne T" sort="Van Der Schouw, Yvonne T" uniqKey="Van Der Schouw Y" first="Yvonne T" last="Van Der Schouw">Yvonne T. Van Der Schouw</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Gils, Carla H" sort="Van Gils, Carla H" uniqKey="Van Gils C" first="Carla H" last="Van Gils">Carla H. Van Gils</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Nierop, Peter" sort="Van Nierop, Peter" uniqKey="Van Nierop P" first="Peter" last="Van Nierop">Peter Van Nierop</name><affiliation><nlm:aff id="A100">Municipal Health Service Brabant-Zuidoost, Helmond, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vink, Jacqueline M" sort="Vink, Jacqueline M" uniqKey="Vink J" first="Jacqueline M" last="Vink">Jacqueline M. Vink</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Visscher, Peter M" sort="Visscher, Peter M" uniqKey="Visscher P" first="Peter M" last="Visscher">Peter M. Visscher</name><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Voorhuis, Marlies" sort="Voorhuis, Marlies" uniqKey="Voorhuis M" first="Marlies" last="Voorhuis">Marlies Voorhuis</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Waeber, Gerard" sort="Waeber, Gerard" uniqKey="Waeber G" first="Gérard" last="Waeber">Gérard Waeber</name><affiliation><nlm:aff id="A102">Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Wallaschofski, Henri" sort="Wallaschofski, Henri" uniqKey="Wallaschofski H" first="Henri" last="Wallaschofski">Henri Wallaschofski</name><affiliation><nlm:aff id="A103">Institute for Clinical Chemistry and Laboratory Medicine, University of Greifswald</nlm:aff></affiliation></author><author><name sortKey="Wichmann, H Erich" sort="Wichmann, H Erich" uniqKey="Wichmann H" first="H Erich" last="Wichmann">H Erich Wichmann</name><affiliation><nlm:aff id="A104">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Klinikum Grosshadern, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Widen, Elisabeth" sort="Widen, Elisabeth" uniqKey="Widen E" first="Elisabeth" last="Widen">Elisabeth Widen</name><affiliation><nlm:aff id="A77">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Gent, Colette Jm Wijnands Van" sort="Gent, Colette Jm Wijnands Van" uniqKey="Gent C" first="Colette Jm Wijnands-Van" last="Gent">Colette Jm Wijnands-Van Gent</name><affiliation><nlm:aff id="A107">POZOB Veldhoven, Veldhoven, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Willemsen, Gonneke" sort="Willemsen, Gonneke" uniqKey="Willemsen G" first="Gonneke" last="Willemsen">Gonneke Willemsen</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wolffenbuttel, Bruce Hr" sort="Wolffenbuttel, Bruce Hr" uniqKey="Wolffenbuttel B" first="Bruce Hr" last="Wolffenbuttel">Bruce Hr Wolffenbuttel</name><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A108">Department of Endocrinology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F" last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Yerges Armstrong, Laura M" sort="Yerges Armstrong, Laura M" uniqKey="Yerges Armstrong L" first="Laura M" last="Yerges-Armstrong">Laura M. Yerges-Armstrong</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Zemunik, Tatijana" sort="Zemunik, Tatijana" uniqKey="Zemunik T" first="Tatijana" last="Zemunik">Tatijana Zemunik</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Zgaga, Lina" sort="Zgaga, Lina" uniqKey="Zgaga L" first="Lina" last="Zgaga">Lina Zgaga</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Zillikens, M Carola" sort="Zillikens, M Carola" uniqKey="Zillikens M" first="M. Carola" last="Zillikens">M. Carola Zillikens</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zygmunt, Marek" sort="Zygmunt, Marek" uniqKey="Zygmunt M" first="Marek" last="Zygmunt">Marek Zygmunt</name><affiliation><nlm:aff id="A110">Klinik für Gynäkologie und Geburtshilfe, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Arnold, Alice M" sort="Arnold, Alice M" uniqKey="Arnold A" first="Alice M" last="Arnold">Alice M. Arnold</name><affiliation><nlm:aff id="A74">Department of Biostatistics, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I" last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">EMGO+ Institute, VU Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Buring, Julie E" sort="Buring, Julie E" uniqKey="Buring J" first="Julie E." last="Buring">Julie E. Buring</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A111">Harvard School of Public Health, Boston, MA USA</nlm:aff></affiliation></author><author><name sortKey="Crisponi, Laura" sort="Crisponi, Laura" uniqKey="Crisponi L" first="Laura" last="Crisponi">Laura Crisponi</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Demerath, Ellen W" sort="Demerath, Ellen W" uniqKey="Demerath E" first="Ellen W" last="Demerath">Ellen W. Demerath</name><affiliation><nlm:aff id="A57">Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Hu, Frank B" sort="Hu, Frank B" uniqKey="Hu F" first="Frank B" last="Hu">Frank B. Hu</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, 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, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Broad Institute of Harvard and MIT, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Estonian Biocenter, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W" last="Montgomery">Grant W. Montgomery</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A" last="Oostra">Ben A. Oostra</name><affiliation><nlm:aff id="A112">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M" last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A111">Harvard School of Public Health, Boston, MA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Division of Cardiology, Brigham and Women’s Hospital, Boston, MA USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Serena" sort="Sanna, Serena" uniqKey="Sanna S" first="Serena" last="Sanna">Serena Sanna</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Schlessinger, David" sort="Schlessinger, David" uniqKey="Schlessinger D" first="David" last="Schlessinger">David Schlessinger</name><affiliation><nlm:aff id="A114">National Institute on Aging, Intramural Research Program, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Streeten, Elizabeth A" sort="Streeten, Elizabeth A" uniqKey="Streeten E" first="Elizabeth A" last="Streeten">Elizabeth A. Streeten</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Uda, Manuela" sort="Uda, Manuela" uniqKey="Uda M" first="Manuela" last="Uda">Manuela Uda</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</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="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="A115">Institut für Community Medicine, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Murray, Anna" sort="Murray, Anna" uniqKey="Murray A" first="Anna" last="Murray">Anna Murray</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Murabito, Joanne M" sort="Murabito, Joanne M" uniqKey="Murabito J" first="Joanne M" last="Murabito">Joanne M. Murabito</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Visser, Jenny A" sort="Visser, Jenny A" uniqKey="Visser J" first="Jenny A" last="Visser">Jenny A. Visser</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lunetta, Kathryn L" sort="Lunetta, Kathryn L" uniqKey="Lunetta K" first="Kathryn L" last="Lunetta">Kathryn L. Lunetta</name><affiliation><nlm:aff id="A28">Department of Biostatistics, Boston University School of Public Health, Boston Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22267201</idno><idno type="pmc">3288642</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288642</idno><idno type="RBID">PMC:3288642</idno><idno type="doi">10.1038/ng.1051</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002E11</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E11</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Meta-analyses identify 13 novel loci associated with age at menopause and highlights DNA repair and immune pathways</title><author><name sortKey="Stolk, Lisette" sort="Stolk, Lisette" uniqKey="Stolk L" first="Lisette" last="Stolk">Lisette Stolk</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Perry, John Rb" sort="Perry, John Rb" uniqKey="Perry J" first="John Rb" last="Perry">John Rb Perry</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="He, Chunyan" sort="He, Chunyan" uniqKey="He C" first="Chunyan" last="He">Chunyan He</name><affiliation><nlm:aff id="A7">Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA</nlm:aff></affiliation></author><author><name sortKey="Mangino, Massimo" sort="Mangino, Massimo" uniqKey="Mangino M" first="Massimo" last="Mangino">Massimo Mangino</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Sulem, Patrick" sort="Sulem, Patrick" uniqKey="Sulem P" first="Patrick" last="Sulem">Patrick Sulem</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Barbalic, Maja" sort="Barbalic, Maja" uniqKey="Barbalic M" first="Maja" last="Barbalic">Maja Barbalic</name><affiliation><nlm:aff id="A11">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Byrne, Enda M" sort="Byrne, Enda M" uniqKey="Byrne E" first="Enda M" last="Byrne">Enda M. Byrne</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Ernst, Florian" sort="Ernst, Florian" uniqKey="Ernst F" first="Florian" last="Ernst">Florian Ernst</name><affiliation><nlm:aff id="A14">Interfakultäres Institut für Genomforschung, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Esko, T Nu" sort="Esko, T Nu" uniqKey="Esko T" first="T Nu" last="Esko">T Nu Esko</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Estonian Biocenter, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Franceschini, Nora" sort="Franceschini, Nora" uniqKey="Franceschini N" first="Nora" last="Franceschini">Nora Franceschini</name><affiliation><nlm:aff id="A18">Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</nlm:aff></affiliation></author><author><name sortKey="Gudbjartsson, Daniel F" sort="Gudbjartsson, Daniel F" uniqKey="Gudbjartsson D" first="Daniel F" last="Gudbjartsson">Daniel F. Gudbjartsson</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Hottenga, Jouke Jan" sort="Hottenga, Jouke Jan" uniqKey="Hottenga J" first="Jouke-Jan" last="Hottenga">Jouke-Jan Hottenga</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Broad Institute of Harvard and MIT, USA</nlm:aff></affiliation></author><author><name sortKey="Mcardle, Patick F" sort="Mcardle, Patick F" uniqKey="Mcardle P" first="Patick F" last="Mcardle">Patick F. Mcardle</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Porcu, Eleonora" sort="Porcu, Eleonora" uniqKey="Porcu E" first="Eleonora" last="Porcu">Eleonora Porcu</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V" last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Van Wingerden, Sophie" sort="Van Wingerden, Sophie" uniqKey="Van Wingerden S" first="Sophie" last="Van Wingerden">Sophie Van Wingerden</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhai, Guangju" sort="Zhai, Guangju" uniqKey="Zhai G" first="Guangju" last="Zhai">Guangju Zhai</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada</nlm:aff></affiliation></author><author><name sortKey="Zhuang, Wei V" sort="Zhuang, Wei V" uniqKey="Zhuang W" first="Wei V" last="Zhuang">Wei V. Zhuang</name><affiliation><nlm:aff id="A28">Department of Biostatistics, Boston University School of Public Health, Boston Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Albrecht, Eva" sort="Albrecht, Eva" uniqKey="Albrecht E" first="Eva" last="Albrecht">Eva Albrecht</name><affiliation><nlm:aff id="A29">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Alizadeh, Behrooz Z" sort="Alizadeh, Behrooz Z" uniqKey="Alizadeh B" first="Behrooz Z" last="Alizadeh">Behrooz Z. Alizadeh</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Bandinelli, Stefania" sort="Bandinelli, Stefania" uniqKey="Bandinelli S" first="Stefania" last="Bandinelli">Stefania Bandinelli</name><affiliation><nlm:aff id="A31">Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy</nlm:aff></affiliation></author><author><name sortKey="Lauc, Lovorka Barac" sort="Lauc, Lovorka Barac" uniqKey="Lauc L" first="Lovorka Barac" last="Lauc">Lovorka Barac Lauc</name><affiliation><nlm:aff id="A32">Croation Science Foundation, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Beckmann, Jacques S" sort="Beckmann, Jacques S" uniqKey="Beckmann J" first="Jacques S" last="Beckmann">Jacques S. Beckmann</name><affiliation><nlm:aff id="A33">Department of Medical Genetics, University of Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Boban, Mladen" sort="Boban, Mladen" uniqKey="Boban M" first="Mladen" last="Boban">Mladen Boban</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="A11">Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Broekmans, Frank J" sort="Broekmans, Frank J" uniqKey="Broekmans F" first="Frank J" last="Broekmans">Frank J. Broekmans</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Burri, Andrea" sort="Burri, Andrea" uniqKey="Burri A" first="Andrea" last="Burri">Andrea Burri</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J" last="Chanock">Stephen J. Chanock</name><affiliation><nlm:aff id="A38">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Chen, Constance" sort="Chen, Constance" uniqKey="Chen C" first="Constance" last="Chen">Constance Chen</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Corre, Tanguy" sort="Corre, Tanguy" uniqKey="Corre T" first="Tanguy" last="Corre">Tanguy Corre</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Coviello, Andrea D" sort="Coviello, Andrea D" uniqKey="Coviello A" first="Andrea D" last="Coviello">Andrea D. Coviello</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="D Damo, Pio" sort="D Damo, Pio" uniqKey="D Damo P" first="Pio" last="D Damo">Pio D Damo</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A44">University of Trieste, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Davies, Gail" sort="Davies, Gail" uniqKey="Davies G" first="Gail" last="Davies">Gail Davies</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="De Faire, Ulf" sort="De Faire, Ulf" uniqKey="De Faire U" first="Ulf" last="De Faire">Ulf De Faire</name><affiliation><nlm:aff id="A46">Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="De Geus, Eco Jc" sort="De Geus, Eco Jc" uniqKey="De Geus E" first="Eco Jc" last="De Geus">Eco Jc De Geus</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">EMGO+ Institute, VU Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Dedoussis, George Vz" sort="Dedoussis, George Vz" uniqKey="Dedoussis G" first="George Vz" last="Dedoussis">George Vz Dedoussis</name><affiliation><nlm:aff id="A49">Department of Nutrition and Dietetics, Harokopio University, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Deloukas, Panagiotis" sort="Deloukas, Panagiotis" uniqKey="Deloukas P" first="Panagiotis" last="Deloukas">Panagiotis Deloukas</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Ebrahim, Shah" sort="Ebrahim, Shah" uniqKey="Ebrahim S" first="Shah" last="Ebrahim">Shah Ebrahim</name><affiliation><nlm:aff id="A50">Department of Epidemiology & Population Healths, London School of Hygiene & Tropical Medicine, UK</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Emilsson, Valur" sort="Emilsson, Valur" uniqKey="Emilsson V" first="Valur" last="Emilsson">Valur Emilsson</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A51">National Institute for Health and Welfare, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A52">Department of General Practice and Primary Health Care, University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A54">Folkhalsan Research Centre, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Vasa Central Hospital, Vasa, Finland</nlm:aff></affiliation></author><author><name sortKey="Fauser, Bart Cjm" sort="Fauser, Bart Cjm" uniqKey="Fauser B" first="Bart Cjm" last="Fauser">Bart Cjm Fauser</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ferreli, Liana" sort="Ferreli, Liana" uniqKey="Ferreli L" first="Liana" last="Ferreli">Liana Ferreli</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Ferrucci, Luigi" sort="Ferrucci, Luigi" uniqKey="Ferrucci L" first="Luigi" last="Ferrucci">Luigi Ferrucci</name><affiliation><nlm:aff id="A56">Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Fischer, Krista" sort="Fischer, Krista" uniqKey="Fischer K" first="Krista" last="Fischer">Krista Fischer</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Folsom, Aaron R" sort="Folsom, Aaron R" uniqKey="Folsom A" first="Aaron R" last="Folsom">Aaron R. Folsom</name><affiliation><nlm:aff id="A57">Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Garcia, Melissa E" sort="Garcia, Melissa E" uniqKey="Garcia M" first="Melissa E" last="Garcia">Melissa E. Garcia</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Gasparini, Paolo" sort="Gasparini, Paolo" uniqKey="Gasparini P" first="Paolo" last="Gasparini">Paolo Gasparini</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A44">University of Trieste, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="A29">Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Glazer, Nicole" sort="Glazer, Nicole" uniqKey="Glazer N" first="Nicole" last="Glazer">Nicole Glazer</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation></author><author><name sortKey="Grobbee, Diederick E" sort="Grobbee, Diederick E" uniqKey="Grobbee D" first="Diederick E" last="Grobbee">Diederick E. Grobbee</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Haller, Toomas" sort="Haller, Toomas" uniqKey="Haller T" first="Toomas" last="Haller">Toomas Haller</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Hankinson, Susan E" sort="Hankinson, Susan E" uniqKey="Hankinson S" first="Susan E" last="Hankinson">Susan E. Hankinson</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Hass, Merli" sort="Hass, Merli" uniqKey="Hass M" first="Merli" last="Hass">Merli Hass</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</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="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Heath, Andrew C" sort="Heath, Andrew C" uniqKey="Heath A" first="Andrew C" last="Heath">Andrew C. Heath</name><affiliation><nlm:aff id="A63">Washington University St.Louis, St. Louis, MO, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ingelsson, Erik" sort="Ingelsson, Erik" uniqKey="Ingelsson E" first="Erik" last="Ingelsson">Erik Ingelsson</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Janssens, A Cecile Jw" sort="Janssens, A Cecile Jw" uniqKey="Janssens A" first="A Cecile Jw" last="Janssens">A Cecile Jw Janssens</name><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D" last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kardia, Sharon Lr" sort="Kardia, Sharon Lr" uniqKey="Kardia S" first="Sharon Lr" last="Kardia">Sharon Lr Kardia</name><affiliation><nlm:aff id="A65">Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Keyzer, Jules" sort="Keyzer, Jules" uniqKey="Keyzer J" first="Jules" last="Keyzer">Jules Keyzer</name><affiliation><nlm:aff id="A66">Diagnostic GP laboratory Eindhoven, Eindhoven, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P" last="Kiel">Douglas P. Kiel</name><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kolcic, Ivana" sort="Kolcic, Ivana" uniqKey="Kolcic I" first="Ivana" last="Kolcic">Ivana Kolcic</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltán" last="Kutalik">Zoltán Kutalik</name><affiliation><nlm:aff id="A33">Department of Medical Genetics, University of Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A67">Swiss Institute of Bioinformatics, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Lahti, Jari" sort="Lahti, Jari" uniqKey="Lahti J" first="Jari" last="Lahti">Jari Lahti</name><affiliation><nlm:aff id="A68">Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Lai, Sandra" sort="Lai, Sandra" uniqKey="Lai S" first="Sandra" last="Lai">Sandra Lai</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Laisk, Triin" sort="Laisk, Triin" uniqKey="Laisk T" first="Triin" last="Laisk">Triin Laisk</name><affiliation><nlm:aff id="A69">Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Laven, Joop Se" sort="Laven, Joop Se" uniqKey="Laven J" first="Joop Se" last="Laven">Joop Se Laven</name><affiliation><nlm:aff id="A70">Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lawlor, Debbie A" sort="Lawlor, Debbie A" uniqKey="Lawlor D" first="Debbie A" last="Lawlor">Debbie A. Lawlor</name><affiliation><nlm:aff id="A71">MRC Centre for Causal Analysis in Translational Epidemiology, School of Social & Community Medicine, University of Bristol, UK</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="A72">Human genetic, Genome Institute of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M" last="Lopez">Lorna M. Lopez</name><affiliation><nlm:aff id="A45">Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Louwers, Yvonne V" sort="Louwers, Yvonne V" uniqKey="Louwers Y" first="Yvonne V" last="Louwers">Yvonne V. Louwers</name><affiliation><nlm:aff id="A70">Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Magnusson, Patrik Ke" sort="Magnusson, Patrik Ke" uniqKey="Magnusson P" first="Patrik Ke" last="Magnusson">Patrik Ke Magnusson</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Marongiu, Mara" sort="Marongiu, Mara" uniqKey="Marongiu M" first="Mara" last="Marongiu">Mara Marongiu</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Klaric, Irena Martinovic" sort="Klaric, Irena Martinovic" uniqKey="Klaric I" first="Irena Martinovic" last="Klaric">Irena Martinovic Klaric</name><affiliation><nlm:aff id="A73">Institute for Migration and Ethnic Studies, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Masciullo, Corrado" sort="Masciullo, Corrado" uniqKey="Masciullo C" first="Corrado" last="Masciullo">Corrado Masciullo</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name><affiliation><nlm:aff id="A74">Department of Biostatistics, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Medland, Sarah E" sort="Medland, Sarah E" uniqKey="Medland S" first="Sarah E" last="Medland">Sarah E. Medland</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Melzer, David" sort="Melzer, David" uniqKey="Melzer D" first="David" last="Melzer">David Melzer</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Mooser, Vincent" sort="Mooser, Vincent" uniqKey="Mooser V" first="Vincent" last="Mooser">Vincent Mooser</name><affiliation><nlm:aff id="A75">Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, USA</nlm:aff></affiliation></author><author><name sortKey="Navarro, Pau" sort="Navarro, Pau" uniqKey="Navarro P" first="Pau" last="Navarro">Pau Navarro</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Newman, Anne B" sort="Newman, Anne B" uniqKey="Newman A" first="Anne B" last="Newman">Anne B. Newman</name><affiliation><nlm:aff id="A76">Departments of Epidemiology and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</nlm:aff></affiliation></author><author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Onland Moret, N Charlotte" sort="Onland Moret, N Charlotte" uniqKey="Onland Moret N" first="N. Charlotte" last="Onland-Moret">N. Charlotte Onland-Moret</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A77">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A78">Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Pare, Guillaume" sort="Pare, Guillaume" uniqKey="Pare G" first="Guillaume" last="Paré">Guillaume Paré</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A79">Genetic and Molecular Epidemiology Laboratory, McMaster University, Hamilton, ON Canada</nlm:aff></affiliation></author><author><name sortKey="Parker, Alex N" sort="Parker, Alex N" uniqKey="Parker A" first="Alex N" last="Parker">Alex N. Parker</name><affiliation><nlm:aff id="A80">Amgen, Cambridge, MA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A81">Foundation Medicine, Inc., Cambridge MA USA</nlm:aff></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L" last="Pedersen">Nancy L. Pedersen</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Peeters, Petra Hm" sort="Peeters, Petra Hm" uniqKey="Peeters P" first="Petra Hm" last="Peeters">Petra Hm Peeters</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Pistis, Giorgio" sort="Pistis, Giorgio" uniqKey="Pistis G" first="Giorgio" last="Pistis">Giorgio Pistis</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Plump, Andrew S" sort="Plump, Andrew S" uniqKey="Plump A" first="Andrew S" last="Plump">Andrew S. Plump</name><affiliation><nlm:aff id="A83">Cardiovascular Disease, Merck Research Laboratory, Rahway, NJ, USA</nlm:aff></affiliation></author><author><name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Pop, Victor Jm" sort="Pop, Victor Jm" uniqKey="Pop V" first="Victor Jm" last="Pop">Victor Jm Pop</name><affiliation><nlm:aff id="A84">Department of Clinical Health Psychology, University of Tilburg, Tilburg, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A85">Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A86">Group Health Research Institute, Group Health Cooperative, Seattle, WA USA</nlm:aff></affiliation></author><author><name sortKey="R Ikkonen, Katri" sort="R Ikkonen, Katri" uniqKey="R Ikkonen K" first="Katri" last="R Ikkönen">Katri R Ikkönen</name><affiliation><nlm:aff id="A68">Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Rehnberg, Emil" sort="Rehnberg, Emil" uniqKey="Rehnberg E" first="Emil" last="Rehnberg">Emil Rehnberg</name><affiliation><nlm:aff id="A60">Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I" last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="A87">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Sala, Cinzia" sort="Sala, Cinzia" uniqKey="Sala C" first="Cinzia" last="Sala">Cinzia Sala</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Salumets, Andres" sort="Salumets, Andres" uniqKey="Salumets A" first="Andres" last="Salumets">Andres Salumets</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A69">Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Scuteri, Angelo" sort="Scuteri, Angelo" uniqKey="Scuteri A" first="Angelo" last="Scuteri">Angelo Scuteri</name><affiliation><nlm:aff id="A89">Lab Cardiovascular Sciences - NIA - NIH, Baltimore, USA</nlm:aff></affiliation></author><author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name><affiliation><nlm:aff id="A90">Laboratory of Neurogenetics, National Institute of Ageing, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A" last="Smith">Jennifer A. Smith</name><affiliation><nlm:aff id="A65">Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stacey, Simon N" sort="Stacey, Simon N" uniqKey="Stacey S" first="Simon N" last="Stacey">Simon N. Stacey</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Geriatric Medicine Unit, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Stathopoulou, Maria G" sort="Stathopoulou, Maria G" uniqKey="Stathopoulou M" first="Maria G" last="Stathopoulou">Maria G. Stathopoulou</name><affiliation><nlm:aff id="A49">Department of Nutrition and Dietetics, Harokopio University, Athens, Greece</nlm:aff></affiliation><affiliation><nlm:aff id="A93">Cardiovascular Genetics Research Unit, EA4373, Université Henri Poincaré - Nancy 1, Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Stirrups, Kathleen" sort="Stirrups, Kathleen" uniqKey="Stirrups K" first="Kathleen" last="Stirrups">Kathleen Stirrups</name><affiliation><nlm:aff id="A24">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</nlm:aff></affiliation></author><author><name sortKey="Stolk, Ronald P" sort="Stolk, Ronald P" uniqKey="Stolk R" first="Ronald P" last="Stolk">Ronald P. Stolk</name><affiliation><nlm:aff id="A30">Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Sun, Yan V" sort="Sun, Yan V" uniqKey="Sun Y" first="Yan V" last="Sun">Yan V. Sun</name><affiliation><nlm:aff id="A94">Department of Epidemiology, Emory University, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Tenesa, Albert" sort="Tenesa, Albert" uniqKey="Tenesa A" first="Albert" last="Tenesa">Albert Tenesa</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A95">The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK</nlm:aff></affiliation></author><author><name sortKey="Thorand, Barbara" sort="Thorand, Barbara" uniqKey="Thorand B" first="Barbara" last="Thorand">Barbara Thorand</name><affiliation><nlm:aff id="A96">Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Toniolo, Daniela" sort="Toniolo, Daniela" uniqKey="Toniolo D" first="Daniela" last="Toniolo">Daniela Toniolo</name><affiliation><nlm:aff id="A40">Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="A97">Institute of Molecular Genetics-CNR, Pavia, Italy</nlm:aff></affiliation></author><author><name sortKey="Tryggvadottir, Laufey" sort="Tryggvadottir, Laufey" uniqKey="Tryggvadottir L" first="Laufey" last="Tryggvadottir">Laufey Tryggvadottir</name><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A98">Icelandic Cancer Registry, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Tsui, Kim" sort="Tsui, Kim" uniqKey="Tsui K" first="Kim" last="Tsui">Kim Tsui</name><affiliation><nlm:aff id="A80">Amgen, Cambridge, MA USA</nlm:aff></affiliation></author><author><name sortKey="Ulivi, Sheila" sort="Ulivi, Sheila" uniqKey="Ulivi S" first="Sheila" last="Ulivi">Sheila Ulivi</name><affiliation><nlm:aff id="A43">Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Van Dam, Rob M" sort="Van Dam, Rob M" uniqKey="Van Dam R" first="Rob M" last="Van Dam">Rob M. Van Dam</name><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Van Der Schouw, Yvonne T" sort="Van Der Schouw, Yvonne T" uniqKey="Van Der Schouw Y" first="Yvonne T" last="Van Der Schouw">Yvonne T. Van Der Schouw</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Gils, Carla H" sort="Van Gils, Carla H" uniqKey="Van Gils C" first="Carla H" last="Van Gils">Carla H. Van Gils</name><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Nierop, Peter" sort="Van Nierop, Peter" uniqKey="Van Nierop P" first="Peter" last="Van Nierop">Peter Van Nierop</name><affiliation><nlm:aff id="A100">Municipal Health Service Brabant-Zuidoost, Helmond, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vink, Jacqueline M" sort="Vink, Jacqueline M" uniqKey="Vink J" first="Jacqueline M" last="Vink">Jacqueline M. Vink</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Visscher, Peter M" sort="Visscher, Peter M" uniqKey="Visscher P" first="Peter M" last="Visscher">Peter M. Visscher</name><affiliation><nlm:aff id="A48">Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A101">Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Voorhuis, Marlies" sort="Voorhuis, Marlies" uniqKey="Voorhuis M" first="Marlies" last="Voorhuis">Marlies Voorhuis</name><affiliation><nlm:aff id="A36">Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A59">Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Waeber, Gerard" sort="Waeber, Gerard" uniqKey="Waeber G" first="Gérard" last="Waeber">Gérard Waeber</name><affiliation><nlm:aff id="A102">Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Wallaschofski, Henri" sort="Wallaschofski, Henri" uniqKey="Wallaschofski H" first="Henri" last="Wallaschofski">Henri Wallaschofski</name><affiliation><nlm:aff id="A103">Institute for Clinical Chemistry and Laboratory Medicine, University of Greifswald</nlm:aff></affiliation></author><author><name sortKey="Wichmann, H Erich" sort="Wichmann, H Erich" uniqKey="Wichmann H" first="H Erich" last="Wichmann">H Erich Wichmann</name><affiliation><nlm:aff id="A104">Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A105">Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A106">Klinikum Grosshadern, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Widen, Elisabeth" sort="Widen, Elisabeth" uniqKey="Widen E" first="Elisabeth" last="Widen">Elisabeth Widen</name><affiliation><nlm:aff id="A77">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Gent, Colette Jm Wijnands Van" sort="Gent, Colette Jm Wijnands Van" uniqKey="Gent C" first="Colette Jm Wijnands-Van" last="Gent">Colette Jm Wijnands-Van Gent</name><affiliation><nlm:aff id="A107">POZOB Veldhoven, Veldhoven, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Willemsen, Gonneke" sort="Willemsen, Gonneke" uniqKey="Willemsen G" first="Gonneke" last="Willemsen">Gonneke Willemsen</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F" last="Wilson">James F. Wilson</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Wolffenbuttel, Bruce Hr" sort="Wolffenbuttel, Bruce Hr" uniqKey="Wolffenbuttel B" first="Bruce Hr" last="Wolffenbuttel">Bruce Hr Wolffenbuttel</name><affiliation><nlm:aff id="A91">LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A108">Department of Endocrinology, University Medical Center Groningen, University of Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F" last="Wright">Alan F. Wright</name><affiliation><nlm:aff id="A62">MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Yerges Armstrong, Laura M" sort="Yerges Armstrong, Laura M" uniqKey="Yerges Armstrong L" first="Laura M" last="Yerges-Armstrong">Laura M. Yerges-Armstrong</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Zemunik, Tatijana" sort="Zemunik, Tatijana" uniqKey="Zemunik T" first="Tatijana" last="Zemunik">Tatijana Zemunik</name><affiliation><nlm:aff id="A35">Faculty of Medicine, University of Split, Split, Croatia</nlm:aff></affiliation></author><author><name sortKey="Zgaga, Lina" sort="Zgaga, Lina" uniqKey="Zgaga L" first="Lina" last="Zgaga">Lina Zgaga</name><affiliation><nlm:aff id="A37">Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A109">Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia</nlm:aff></affiliation></author><author><name sortKey="Zillikens, M Carola" sort="Zillikens, M Carola" uniqKey="Zillikens M" first="M. Carola" last="Zillikens">M. Carola Zillikens</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zygmunt, Marek" sort="Zygmunt, Marek" uniqKey="Zygmunt M" first="Marek" last="Zygmunt">Marek Zygmunt</name><affiliation><nlm:aff id="A110">Klinik für Gynäkologie und Geburtshilfe, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Arnold, Alice M" sort="Arnold, Alice M" uniqKey="Arnold A" first="Alice M" last="Arnold">Alice M. Arnold</name><affiliation><nlm:aff id="A74">Department of Biostatistics, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I" last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A19">Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A47">EMGO+ Institute, VU Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Buring, Julie E" sort="Buring, Julie E" uniqKey="Buring J" first="Julie E." last="Buring">Julie E. Buring</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A111">Harvard School of Public Health, Boston, MA USA</nlm:aff></affiliation></author><author><name sortKey="Crisponi, Laura" sort="Crisponi, Laura" uniqKey="Crisponi L" first="Laura" last="Crisponi">Laura Crisponi</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Demerath, Ellen W" sort="Demerath, Ellen W" uniqKey="Demerath E" first="Ellen W" last="Demerath">Ellen W. Demerath</name><affiliation><nlm:aff id="A57">Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A25">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Hu, Frank B" sort="Hu, Frank B" uniqKey="Hu F" first="Frank B" last="Hu">Frank B. Hu</name><affiliation><nlm:aff id="A20">Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, 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, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Broad Institute of Harvard and MIT, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A58">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Metspalu, Andres" sort="Metspalu, Andres" uniqKey="Metspalu A" first="Andres" last="Metspalu">Andres Metspalu</name><affiliation><nlm:aff id="A15">Estonian Genome Center, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Estonian Biocenter, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</nlm:aff></affiliation><affiliation><nlm:aff id="A88">Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia</nlm:aff></affiliation></author><author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W" last="Montgomery">Grant W. Montgomery</name><affiliation><nlm:aff id="A13">Queensland Institute of Medical Research, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A" last="Oostra">Ben A. Oostra</name><affiliation><nlm:aff id="A112">Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M" last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="A5">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A111">Harvard School of Public Health, Boston, MA USA</nlm:aff></affiliation><affiliation><nlm:aff id="A113">Division of Cardiology, Brigham and Women’s Hospital, Boston, MA USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Serena" sort="Sanna, Serena" uniqKey="Sanna S" first="Serena" last="Sanna">Serena Sanna</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Schlessinger, David" sort="Schlessinger, David" uniqKey="Schlessinger D" first="David" last="Schlessinger">David Schlessinger</name><affiliation><nlm:aff id="A114">National Institute on Aging, Intramural Research Program, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D" last="Spector">Tim D. Spector</name><affiliation><nlm:aff id="A9">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Streeten, Elizabeth A" sort="Streeten, Elizabeth A" uniqKey="Streeten E" first="Elizabeth A" last="Streeten">Elizabeth A. Streeten</name><affiliation><nlm:aff id="A22">Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A10">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Uda, Manuela" sort="Uda, Manuela" uniqKey="Uda M" first="Manuela" last="Uda">Manuela Uda</name><affiliation><nlm:aff id="A23">Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</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="A2">Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="A115">Institut für Community Medicine, Universität Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Murray, Anna" sort="Murray, Anna" uniqKey="Murray A" first="Anna" last="Murray">Anna Murray</name><affiliation><nlm:aff id="A3">Peninsula Medical School, University of Exeter, UK</nlm:aff></affiliation></author><author><name sortKey="Murabito, Joanne M" sort="Murabito, Joanne M" uniqKey="Murabito J" first="Joanne M" last="Murabito">Joanne M. Murabito</name><affiliation><nlm:aff id="A41">Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Visser, Jenny A" sort="Visser, Jenny A" uniqKey="Visser J" first="Jenny A" last="Visser">Jenny A. Visser</name><affiliation><nlm:aff id="A1">Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lunetta, Kathryn L" sort="Lunetta, Kathryn L" uniqKey="Lunetta K" first="Kathryn L" last="Lunetta">Kathryn L. Lunetta</name><affiliation><nlm:aff id="A28">Department of Biostatistics, Boston University School of Public Health, Boston Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A42">NHLBI Framingham Heart Study, Framingham, MA, USA</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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci (<italic>P</italic> < 5 × 10<sup>−8</sup>). The new loci included genes implicated in DNA repair (<italic>EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1</italic>) and immune function (<italic>IL11, NLRP11, BAT2</italic>). Gene-set enrichment pathway analyses using the full GWAS dataset identified exodeoxyribonuclease, NFκB signalling and mitochondrial dysfunction as biological processes related to timing of menopause.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Burger, Hg" uniqKey="Burger H">HG Burger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Broekmans, Fj" uniqKey="Broekmans F">FJ Broekmans</name></author><author><name sortKey="Soules, Mr" uniqKey="Soules M">MR Soules</name></author><author><name sortKey="Fauser, Bc" uniqKey="Fauser B">BC Fauser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Te Velde, Er" uniqKey="Te Velde E">ER te Velde</name></author><author><name sortKey="Pearson, Pl" uniqKey="Pearson P">PL Pearson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Te Velde, Er" uniqKey="Te Velde E">ER te 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<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">22267201</article-id><article-id pub-id-type="pmc">3288642</article-id><article-id pub-id-type="doi">10.1038/ng.1051</article-id><article-id pub-id-type="manuscript">NIHMS342040</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Meta-analyses identify 13 novel loci associated with age at menopause and highlights DNA repair and immune pathways</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Stolk</surname><given-names>Lisette</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Perry</surname><given-names>John RB</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Chasman</surname><given-names>Daniel I</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Chunyan</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Mangino</surname><given-names>Massimo</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Sulem</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Barbalic</surname><given-names>Maja</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Broer</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Byrne</surname><given-names>Enda M</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Ernst</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Esko</surname><given-names>Tõnu</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Franceschini</surname><given-names>Nora</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib 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rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Thorsteinsdottir</surname><given-names>Unnur</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Uda</surname><given-names>Manuela</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Uitterlinden</surname><given-names>André G</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Völzke</surname><given-names>Henry</given-names></name><xref ref-type="aff" rid="A115">115</xref></contrib><contrib contrib-type="author"><name><surname>Murray</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN3" ref-type="author-notes">#</xref></contrib><contrib contrib-type="author"><name><surname>Murabito</surname><given-names>Joanne M</given-names></name><xref ref-type="aff" rid="A41">41</xref><xref ref-type="aff" rid="A42">42</xref><xref rid="FN3" ref-type="author-notes">#</xref></contrib><contrib contrib-type="author"><name><surname>Visser</surname><given-names>Jenny A</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>Lunetta</surname><given-names>Kathryn L</given-names></name><xref ref-type="aff" rid="A28">28</xref><xref ref-type="aff" rid="A42">42</xref><xref rid="FN3" ref-type="author-notes">#</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands</aff><aff id="A2"><label>2</label>Netherlands Consortium of Healthy Aging, Rotterdam, the Netherlands</aff><aff id="A3"><label>3</label>Peninsula Medical School, University of Exeter, UK</aff><aff id="A4"><label>4</label>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</aff><aff id="A5"><label>5</label>Division of Preventive Medicine, Brigham and Women’s Hospital, Boston USA</aff><aff id="A6"><label>6</label>Harvard Medical School, Boston, USA</aff><aff id="A7"><label>7</label>Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, USA</aff><aff id="A8"><label>8</label>Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA</aff><aff id="A9"><label>9</label>Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</aff><aff id="A10"><label>10</label>deCODE Genetics, Reykjavik, Iceland</aff><aff id="A11"><label>11</label>Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA</aff><aff id="A12"><label>12</label>Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A13"><label>13</label>Queensland Institute of Medical Research, Brisbane, Australia</aff><aff id="A14"><label>14</label>Interfakultäres Institut für Genomforschung, Universität Greifswald, Germany</aff><aff id="A15"><label>15</label>Estonian Genome Center, University of Tartu, Tartu, Estonia</aff><aff id="A16"><label>16</label>Estonian Biocenter, Tartu, Estonia</aff><aff id="A17"><label>17</label>Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</aff><aff id="A18"><label>18</label>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA</aff><aff id="A19"><label>19</label>Dept Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands</aff><aff id="A20"><label>20</label>Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA</aff><aff id="A21"><label>21</label>Broad Institute of Harvard and MIT, USA</aff><aff id="A22"><label>22</label>Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA</aff><aff id="A23"><label>23</label>Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy</aff><aff id="A24"><label>24</label>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK</aff><aff id="A25"><label>25</label>Icelandic Heart Association, Kopavogur, Iceland</aff><aff id="A26"><label>26</label>Faculty of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="A27"><label>27</label>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada</aff><aff id="A28"><label>28</label>Department of Biostatistics, Boston University School of Public Health, Boston Massachusetts, USA</aff><aff id="A29"><label>29</label>Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A30"><label>30</label>Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands</aff><aff id="A31"><label>31</label>Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy</aff><aff id="A32"><label>32</label>Croation Science Foundation, Zagreb, Croatia</aff><aff id="A33"><label>33</label>Department of Medical Genetics, University of Lausanne, Switzerland</aff><aff id="A34"><label>34</label>Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</aff><aff id="A35"><label>35</label>Faculty of Medicine, University of Split, Split, Croatia</aff><aff id="A36"><label>36</label>Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands</aff><aff id="A37"><label>37</label>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK</aff><aff id="A38"><label>38</label>Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA</aff><aff id="A39"><label>39</label>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA</aff><aff id="A40"><label>40</label>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy</aff><aff id="A41"><label>41</label>Sections of General Internal Medicine, Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston MA, USA</aff><aff id="A42"><label>42</label>NHLBI Framingham Heart Study, Framingham, MA, USA</aff><aff id="A43"><label>43</label>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo” Trieste, Italy</aff><aff id="A44"><label>44</label>University of Trieste, Trieste, Italy</aff><aff id="A45"><label>45</label>Department of Psychology, The University of Edinburgh, Edinburgh, UK</aff><aff id="A46"><label>46</label>Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden</aff><aff id="A47"><label>47</label>EMGO+ Institute, VU Medical Centre, Amsterdam, The Netherlands</aff><aff id="A48"><label>48</label>Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK</aff><aff id="A49"><label>49</label>Department of Nutrition and Dietetics, Harokopio University, Athens, Greece</aff><aff id="A50"><label>50</label>Department of Epidemiology & Population Healths, London School of Hygiene & Tropical Medicine, UK</aff><aff id="A51"><label>51</label>National Institute for Health and Welfare, Finland</aff><aff id="A52"><label>52</label>Department of General Practice and Primary Health Care, University of Helsinki, Finland</aff><aff id="A53"><label>53</label>Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland</aff><aff id="A54"><label>54</label>Folkhalsan Research Centre, Helsinki, Finland</aff><aff id="A55"><label>55</label>Vasa Central Hospital, Vasa, Finland</aff><aff id="A56"><label>56</label>Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA</aff><aff id="A57"><label>57</label>Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</aff><aff id="A58"><label>58</label>Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD, USA</aff><aff id="A59"><label>59</label>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</aff><aff id="A60"><label>60</label>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</aff><aff id="A61"><label>61</label>Channing Laboratory, Department of Medicine, Brigham and Women.s Hospital Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A62"><label>62</label>MRC Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK</aff><aff id="A63"><label>63</label>Washington University St.Louis, St. Louis, MO, USA</aff><aff id="A64"><label>64</label>Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A65"><label>65</label>Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA</aff><aff id="A66"><label>66</label>Diagnostic GP laboratory Eindhoven, Eindhoven, the Netherlands</aff><aff id="A67"><label>67</label>Swiss Institute of Bioinformatics, Switzerland</aff><aff id="A68"><label>68</label>Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland</aff><aff id="A69"><label>69</label>Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia</aff><aff id="A70"><label>70</label>Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Erasmus MC, Rotterdam, the Netherlands</aff><aff id="A71"><label>71</label>MRC Centre for Causal Analysis in Translational Epidemiology, School of Social & Community Medicine, University of Bristol, UK</aff><aff id="A72"><label>72</label>Human genetic, Genome Institute of Singapore, Singapore</aff><aff id="A73"><label>73</label>Institute for Migration and Ethnic Studies, Zagreb, Croatia</aff><aff id="A74"><label>74</label>Department of Biostatistics, University of Washington, Seattle, WA, USA</aff><aff id="A75"><label>75</label>Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, USA</aff><aff id="A76"><label>76</label>Departments of Epidemiology and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</aff><aff id="A77"><label>77</label>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland</aff><aff id="A78"><label>78</label>Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland</aff><aff id="A79"><label>79</label>Genetic and Molecular Epidemiology Laboratory, McMaster University, Hamilton, ON Canada</aff><aff id="A80"><label>80</label>Amgen, Cambridge, MA USA</aff><aff id="A81"><label>81</label>Foundation Medicine, Inc., Cambridge MA USA</aff><aff id="A82"><label>82</label>Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK</aff><aff id="A83"><label>83</label>Cardiovascular Disease, Merck Research Laboratory, Rahway, NJ, USA</aff><aff id="A84"><label>84</label>Department of Clinical Health Psychology, University of Tilburg, Tilburg, the Netherlands</aff><aff id="A85"><label>85</label>Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA USA</aff><aff id="A86"><label>86</label>Group Health Research Institute, Group Health Cooperative, Seattle, WA USA</aff><aff id="A87"><label>87</label>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA</aff><aff id="A88"><label>88</label>Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia</aff><aff id="A89"><label>89</label>Lab Cardiovascular Sciences - NIA - NIH, Baltimore, USA</aff><aff id="A90"><label>90</label>Laboratory of Neurogenetics, National Institute of Ageing, Bethesda, MD, USA</aff><aff id="A91"><label>91</label>LifeLines Cohort Study & Biobank, University Medical Center Groningen, University of Groningen, the Netherlands</aff><aff id="A92"><label>92</label>Geriatric Medicine Unit, University of Edinburgh, Edinburgh, UK</aff><aff id="A93"><label>93</label>Cardiovascular Genetics Research Unit, EA4373, Université Henri Poincaré - Nancy 1, Nancy, France</aff><aff id="A94"><label>94</label>Department of Epidemiology, Emory University, Atlanta, GA, USA</aff><aff id="A95"><label>95</label>The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK</aff><aff id="A96"><label>96</label>Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A97"><label>97</label>Institute of Molecular Genetics-CNR, Pavia, Italy</aff><aff id="A98"><label>98</label>Icelandic Cancer Registry, Reykjavik, Iceland</aff><aff id="A99"><label>99</label>Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</aff><aff id="A100"><label>100</label>Municipal Health Service Brabant-Zuidoost, Helmond, the Netherlands</aff><aff id="A101"><label>101</label>Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia</aff><aff id="A102"><label>102</label>Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), University Hospital, Lausanne, Switzerland</aff><aff id="A103"><label>103</label>Institute for Clinical Chemistry and Laboratory Medicine, University of Greifswald</aff><aff id="A104"><label>104</label>Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</aff><aff id="A105"><label>105</label>Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</aff><aff id="A106"><label>106</label>Klinikum Grosshadern, Munich, Germany</aff><aff id="A107"><label>107</label>POZOB Veldhoven, Veldhoven, the Netherlands</aff><aff id="A108"><label>108</label>Department of Endocrinology, University Medical Center Groningen, University of Groningen, the Netherlands</aff><aff id="A109"><label>109</label>Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia</aff><aff id="A110"><label>110</label>Klinik für Gynäkologie und Geburtshilfe, Universität Greifswald, Germany</aff><aff id="A111"><label>111</label>Harvard School of Public Health, Boston, MA USA</aff><aff id="A112"><label>112</label>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A113"><label>113</label>Division of Cardiology, Brigham and Women’s Hospital, Boston, MA USA</aff><aff id="A114"><label>114</label>National Institute on Aging, Intramural Research Program, Baltimore, MD, USA</aff><aff id="A115"><label>115</label>Institut für Community Medicine, Universität Greifswald, Germany</aff><author-notes><corresp id="FN1">Corresponding authors: Anna Murray, Peninsula Medical School, St Lukes, Magdalen Road, Exeter, EX1 2LU, UK, <email>anna.murray@pms.ac.uk</email>. Kathryn L Lunetta, Department of Biostatistics, Boston University School of Public Health, 801 Mass Avenue, Crosstown Center, CT313, Boston, MA 02118, <email>klunetta@bu.edu</email></corresp><fn id="FN2"><label>*</label><p>These authors contributed jointly to this work</p></fn><fn id="FN3"><label>#</label><p>These senior authors jointly oversaw this work</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>13</day><month>12</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>22</day><month>1</month><year>2012</year></pub-date><pub-date pub-type="collection"><month>3</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>9</month><year>2012</year></pub-date><volume>44</volume><issue>3</issue><fpage>260</fpage><lpage>268</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ng.1051</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
<uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri></license-p></license></permissions><abstract><p id="P1">To identify novel loci for age at natural menopause, we performed a meta-analysis of 22 genome-wide association studies in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 new age at natural menopause loci (<italic>P</italic> < 5 × 10<sup>−8</sup>). The new loci included genes implicated in DNA repair (<italic>EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1</italic>) and immune function (<italic>IL11, NLRP11, BAT2</italic>). Gene-set enrichment pathway analyses using the full GWAS dataset identified exodeoxyribonuclease, NFκB signalling and mitochondrial dysfunction as biological processes related to timing of menopause.</p></abstract></article-meta></front><body><sec sec-type="intro" id="S1"><title>Introduction</title><p id="P2">Menopause is the cessation of reproductive function of the human ovaries. This life stage is associated with one of the major hormonal changes of women characterized by a decline in secretion of estrogen, progesterone and, to a lesser degree, testosterone. It influences a woman’s well-being and is associated with several major age-related diseases including cardiovascular disease, breast cancer, osteoarthritis, and osteoporosis<sup><xref rid="R1" ref-type="bibr">1</xref></sup>. Ovarian aging is reflected by the continuous decline of the primordial follicle pool, which is established during fetal life, subsequently leading to endocrine changes due to loss of the negative feedback from ovarian hormones on the hypothalamic-pituitary axis. In addition to follicle loss, oocyte quality diminishes with increasing age, which is believed to be due to increased meiotic nondisjunction<sup><xref rid="R2" ref-type="bibr">2</xref></sup>. Oocyte quality may be controlled at the time germ cells are formed during fetal life, but may also reflect accumulated damage during reproductive life, and/or age-related changes in granulosa cell-oocyte communication<sup><xref rid="R3" ref-type="bibr">3</xref></sup>. Although both oocyte quantity and quality decline with increasing age, it is not clear whether they are controlled by the same mechanisms and whether they decline in parallel.</p><p id="P3">The average age at natural menopause in women of Northern European descent is 50–51 years (range 40–60 years)<sup><xref rid="R4" ref-type="bibr">4</xref></sup>. Heritability estimates from twin and family studies for age at natural menopause range from 44 to 65%<sup><xref rid="R5" ref-type="bibr">5</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup>. Thus far most genetic association studies regarding age at menopause have focussed on candidate genes<sup><xref rid="R9" ref-type="bibr">9</xref></sup> from the estrogen pathway<sup><xref rid="R10" ref-type="bibr">10</xref>,<xref rid="R11" ref-type="bibr">11</xref></sup>, or vascular components<sup><xref rid="R12" ref-type="bibr">12</xref>,<xref rid="R13" ref-type="bibr">13</xref></sup>. Recently two genome-wide association studies (GWAS) identified five novel loci associated with age at natural menopause on chromosomes 5, 6, 13, 19 and 20<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R15" ref-type="bibr">15</xref></sup>. These loci, however, explained <1.5% of the phenotypic variation of age at natural menopause, suggesting additional loci of small effect are likely to be discovered in larger samples. Therefore, we conducted a two-stage GWAS of women of European ancestry, combining the women from the two previous GWAS studies<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R15" ref-type="bibr">15</xref></sup> with new participants for a total of 38,968 women from 22 studies in the discovery stage, and 14,435 women from 21 studies in the replication stage.</p></sec><sec sec-type="results" id="S2"><title>Results</title><p id="P4">In our discovery stage of 38,968 women with natural menopause between the ages of 40 and 60 (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 1</xref>, <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>), we identified 20 regions with SNPs meeting the genome-wide significance criterion p<5 × 10<sup>−8</sup> (<xref rid="F1" ref-type="fig">Figure 1a</xref>). Four of these loci confirmed prior reports of associations on chromosomes 5, 6, 19, and 20<sup><xref rid="R14" ref-type="bibr">14</xref>,<xref rid="R15" ref-type="bibr">15</xref></sup> (regions 5b, 6a, 19a, and 20, respectively, in <xref rid="T1" ref-type="table">Table 1</xref>) and 16 loci were novel. We failed to confirm one previously reported association on chromosome 13 (13q34, rs7333181, p=0.12). The overall genomic inflation factor was 1.03 (<xref rid="F1" ref-type="fig">Figure 1b</xref>). <xref rid="T1" ref-type="table">Table 1</xref> displays the SNP with the lowest p-value from each region. There was no between-study effect heterogeneity across discovery studies (p>0.05/20) for the 20 SNP associations presented. Within FHS, we tested for differences in effect size for the 20 SNPs in retrospectively and prospectively collected menopause age, and also found no significant differences (data not shown). The effect sizes ranged from 0.17 years (8.7 weeks) to nearly one year (50.5 weeks) per each copy of the minor allele. We computed the effect sizes for dichotomized age at natural menopause in the WGHS women, dichotomizing at age 45 (N=745) versus later for early menopause and at 54 (N=1632) versus earlier for late menopause. The estimated odds ratios for early menopause for the menopause decreasing allele ranged from 1.01 to 2.03. The estimated odds ratios for late menopause for the menopause decreasing allele ranged from 0.52 to 0.96 (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 3</xref>). The top SNPs in regions 2c, 5a, and 19b were more than 400kb but less than 1Mb from the top SNP in another region on the same chromosome. The top SNP in each of these primary regions had low linkage disequilibrium (r<sup>2</sup><0.5) with the top SNP in the nearby region. To determine whether these associations were independent, we performed a conditional association analysis in the discovery study samples with the most significant SNP from each of the primary 17 regions included as covariates in the analysis. For regions 5a and 19b (rs890835, rs12461110), the effect estimates in the conditional analysis were unchanged compared to the discovery analysis (differences of 0.3% and 4%, respectively), and the p-values remained genome-wide significant. However, for region 2c the effect size was decreased by ~12.5% in the conditional analysis compared to the initial analysis, and the SNP p-value was no longer genome-wide significant (p=9.8×10<sup>−7</sup>) (<xref rid="T1" ref-type="table">Table 1</xref>), suggesting that the association with rs7606918 is not independent of the rs1018348 region 2b association. We attempted replication only for the 19 SNPs that represented independent regions that reached genome-wide significance (p<5 × 10<sup>−8</sup>) thus replication of rs7606918 was not pursued.</p><sec id="S3"><title>Replication</title><p id="P5">Twenty-one studies contributed 14,435 women for replication of the 19 SNPs defining the independent genome-wide significant regions from stage 1. Age at natural menopause was defined using the same criteria as in the discovery studies (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 1</xref>). Seventeen of these studies (N=6,639) were included in <italic>in silico</italic> replication (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>); an additional 4 studies (N=7,796) contributed <italic>de novo</italic> genotypes for the 19 SNPs (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>). <xref rid="T1" ref-type="table">Table 1</xref> displays the effect sizes and p-values for replication and a combined meta-analysis of the discovery and replication samples. There was no evidence for effect heterogeneity among the replication studies (<xref rid="T1" ref-type="table">Table 1</xref>). Further, we tested for heterogeneity between the <italic>in silico</italic> and <italic>de novo</italic> genotyped studies, and found no evidence for heterogeneity of effect (data not shown), suggesting that for the significant SNPs, the genotype imputation methods did not result in significantly different effect size estimates than would have been obtained from direct genotyping. Seventeen of the 19 SNPs remained genome-wide significant and had lower p-values in combined meta-analysis of the discovery and replication samples. Regions 5a and 13a showed no evidence of association in the replication samples (p>0.50) and were not genome-wide significant in combined discovery and replication meta-analysis. Four of the 17 replicated regions were reported previously; thus our analysis identified 13 novel regions for age at natural menopause based on genome-wide significant discovery with replication. In the combined discovery and replication meta-analyses the effect estimates ranged from 8.2 to 49.3 weeks per minor allele. The estimated proportion of variance explained by the 17 replicated SNPs in the four replication studies with <italic>de novo</italic> genotyped SNPs ranged from 2.5% (Osteos) to 3.7% (EPOS and BWHHS) to 4.1% (PROSPECT-EPIC).</p><p id="P6">We used the largest study contributing data to our discovery GWAS (WGHS, N=11379) to explore whether substantial SNPxSNP interactions are present among the 17 replicated SNPs. We tested all 136 pairs of SNPs and found no evidence for interaction (all P>0.01).</p></sec><sec id="S4"><title>Roles of genes at/near novel loci</title><p id="P7">All but two of the replicated SNPs are intronic or exonic to known genes (<xref rid="T2" ref-type="table">Table 2</xref>). The top SNPs in regions 6b, 12, 19b, and 20 are missense polymorphisms. Three of the four were predicted to have damaging protein function by SIFT<sup><xref rid="R16" ref-type="bibr">16</xref></sup>, and one by PolyPhen2<sup><xref rid="R17" ref-type="bibr">17</xref></sup>. Using dbSNP and LocusZoom<sup><xref rid="R18" ref-type="bibr">18</xref></sup>, we identified the genes underlying the novel top regions. We used SCAN (see URLs) to identify all genes with SNPs that are in linkage disequilibrium (LD) (r<sup>2</sup>>0.5) with our SNPs (<xref rid="T2" ref-type="table">Table 2</xref>). We identified all SNPs with r<sup>2</sup> ≥ 0.8 with our top SNPs and used several databases to determine if the SNPs were known to be associated with expression (<xref rid="T2" ref-type="table">Table 2</xref>).</p><p id="P8">The strongest novel signal was on chromosome 4 (region 4, rs4693089; P=2.4×10<sup>−19</sup>). The SNP is located in an intron of <italic>HELQ</italic>, the gene that encodes the protein HEL308, which is a DNA-dependent ATPase and DNA helicase <sup><xref rid="R19" ref-type="bibr">19</xref></sup>. The second strongest novel signal was on chromosome 12 (region 12, rs2277339; P=2.5×10<sup>−19</sup>). This SNP is a non-synonymous variant in exon 1 of <italic>PRIM1</italic>. The top SNP was significantly associated with expression of <italic>PRIM1</italic> in visual cortex, cerebellum, and pre-frontal cortex (<xref rid="T2" ref-type="table">Table 2</xref>).</p><p id="P9">Several other novel signals are located in introns of genes for which mouse models exist. These were region 8 in <italic>ASH2L</italic> (rs2517388; P=9.3×10<sup>−15</sup>), region 13b in <italic>POLG</italic> (rs2307449; P=3.6×10<sup>−13</sup>) and region 1b in <italic>EXO1</italic> (rs1635501; P=8.5×10<sup>−10</sup>). <italic>ASH2L</italic> codes for a trithorax group protein, and is involved in X chromosome inactivation in women<sup><xref rid="R20" ref-type="bibr">20</xref></sup>. <italic>POLG</italic> encodes the catalytic subunit of mitochondrial DNA polymerase, the enzyme responsible for replication and repair<sup><xref rid="R21" ref-type="bibr">21</xref></sup> of mitochondrial DNA. <italic>EXO1</italic> is a member of the RAD2 nuclease family of proteins involved in DNA replication, repair and recombination, and the top hit is in LD (r<sup>2</sup>=0.83) with a functional polymorphism in <italic>EXO1</italic> that affects a transcription factor binding site in the promoter. Region 11 (rs12294104; P=1.5×10<sup>−11</sup>) is near and in LD (r<sup>2</sup>=0.92) with SNPs in <italic>FSHB</italic>. Transcription of <italic>FSHB</italic> limits the rate of production of the heterodimeric follicle stimulating hormone (FSH), a key pituitary expressed hormone that stimulates maturation of follicles. Region 19a (rs11668344; P=1.5×10<sup>−59</sup>) is in tight LD with SNPs in <italic>IL11</italic>: this cytokine stimulates the T-cell-dependent development of immunoglobulin-producing B cells.</p><p id="P10">The top SNPs in two other novel regions are non-synonymous coding variants. Region 6b, rs1046089 (P=1.6×10<sup>−16</sup>) is in exon 22 of <italic>BAT2</italic> and was associated with expression of several transcripts in the HLA region in several tissues (<xref rid="T2" ref-type="table">Table 2</xref>). Region 19b, rs12461110 (P=8.7 × 10<sup>−10</sup>) is in exon 5 of <italic>NLRP11. BAT2</italic> encodes the gene for HLA-B associated transcript 2 and has several microsatellite repeats. <italic>NLRP11</italic> encodes for the NLR family, pyrin domain containing 11 protein, which is implicated in the activation of proinflammatory caspases<sup><xref rid="R22" ref-type="bibr">22</xref></sup>.</p><p id="P11">Of the remaining five novel regions, the top SNPs for regions 1a, 2a, 2b, and 13b are located in introns. These were rs4246511 in <italic>RHBDL2</italic> (0.24 years/minor allele, P=9.1×10<sup>−17</sup>), which is thought to function as intramembrane serine proteases, rs2303369 in <italic>FNDC4</italic> coding for fibronectin type III domain containing 4 (P=2.3×10<sup>−12</sup>), rs10183486 in <italic>TLK1</italic> (P=2.2×10<sup>−14</sup>) a nuclear serine/threonine kinases that is potentially involved in the regulation of chromatin assembly, and rs4886238 in <italic>TDRD3</italic> (P=9.5×10<sup>−11</sup>). <italic>TDRD3</italic> is a known binding partner for <italic>FMR1</italic>, which has been associated with primary ovarian insufficiency. The top SNP in the final novel region, 16, is within 60kb of three genes: <italic>TNFRSF17, GSPT1</italic>, and <italic>RUNDC2A</italic>. It is in LD (r<sup>2</sup>>0.5) with SNPs in these three genes as well as four others (rs10852344; P=1.0×10<sup>−11</sup>) (<xref rid="T2" ref-type="table">Table 2</xref>).</p></sec><sec id="S5"><title>Pathway analyses</title><p id="P12">We used three independent pathway-based methods to identify connections among our single marker associations, and link them with broader biological processes. While all three approaches (Ingenuity Pathway Analysis(IPA, see URLs), MAGENTA<sup><xref rid="R23" ref-type="bibr">23</xref></sup> and GRAIL<sup><xref rid="R24" ref-type="bibr">24</xref></sup>) are based on published data, linking the gene products of our top hits to each other in functional pathways, each uses substantially different methodology and take different aspects of our results as input. Thus, we expect complementary results from the three approaches.</p><p id="P13">We used IPA(See URLs), to identify potential biological pathways common to the 17 replicated SNPs. Based on the genes physically nearest the 17 loci, four major functional networks were identified based on direct interactions only (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). Network 1, related to “lipid metabolism, molecular transport, and small molecule biochemistry”, contained 14 of the genes nearest to the menopause loci (P=1×10<sup>−30</sup>). Central to this network is the <italic>HNF4A</italic> gene, which is known to play a role in diabetes. Network 2, containing 12 of the input genes, relates to “cell cycle, cell death, and cancer” (P=1×10<sup>−24</sup>). The <italic>ESR1</italic> gene is central in this network, suggesting that genes in this network influence or are influenced by estrogen signaling. Network 3, also in part related to “cell death”, including TNF and NFκB (P=1×10<sup>−19</sup>). Network 4 relates to “infection mechanism, DNA replication, recombination, and repair, and gene expression” (P=1×10<sup>−12</sup>). Interestingly, several of the input genes included in network 1 (<italic>EXO1, HELQ</italic>) and network 2 (<italic>UIMC1, FANCI, TLK1</italic>) are also involved in DNA repair mechanisms.</p><p id="P14">We used a gene set enrichment analysis (GSEA) implemented in MAGENTA<sup><xref rid="R23" ref-type="bibr">23</xref></sup> to explore pathway-based associations using the full GWAS results. Three pathways reached study-wide significance (FDR < 0.05): exodeoxyribonuclease (P = 0.0005), NFκB signalling (P = 0.0006) and mitochondrial dysfunction (P = 0.0001) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>).</p><p id="P15">Finally, we used the GRAIL method of literature based pathway analysis<sup><xref rid="R24" ref-type="bibr">24</xref></sup> to explore the connections between the genes near our top SNPs. Genes are considered related if they share informative words. GRAIL scores for genes associated with 3 of the replicating genome-wide significant SNPs were significant: <italic>EXO1, FKBPL</italic>, and <italic>BRSK1</italic>. When applied to a deeper set of 66 SNPs from the discovery meta-analysis with significance meeting FDR<0.05, 12 genes had significant GRAIL scores: <italic>EXO1, MSH6, PARL, RHBDL2, FKBPL, TP53BP1, TLK1, RAD54L, CHEK2, H2AFX, APEX1, REV3L</italic>. In addition, <italic>BRSK1</italic> was borderline significant with GRAIL FDR=0.06.</p></sec><sec id="S6"><title>Candidate genes</title><p id="P16">Within the discovery GWAS 18,327 SNPs were within 60kb of the start and end of transcription of 125 candidate genes selected because of a reported relationship with ovarian function (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 6</xref>). After multiple testing correction, 101 SNPs in or near five of the candidate genes (<italic>DMC1, EIF2B4, FSHB, POLG, RFPL4A</italic>) were significantly associated with age at natural menopause after multiple testing correction. SNPs in or near four of these genes were already identified as genome-wide significant (<italic>EIF2B4</italic>, region 2a; <italic>RFPL4A</italic>, region 19b; <italic>POLG</italic>, region 15; and <italic>FSHB</italic>, region 11). For the other gene, <italic>DMC1</italic>, the most significant SNP was rs763121, with nominal P=1.6×10<sup>−7</sup>, (P=0.0009 corrected for candidate gene SNP analyses); age at natural menopause decreases by ~0.18 years per copy of the minor allele. <italic>DMC1</italic> encodes for a protein that is essential for meiotic homologous recombination and is regulated by <italic>NOBOX</italic>, mutations in which can cause Primary Ovarian Insufficiency (POI)<sup><xref rid="R25" ref-type="bibr">25</xref>–<xref rid="R27" ref-type="bibr">27</xref></sup></p></sec><sec id="S7"><title>Pleiotropy of primary hits</title><p id="P17">We examined overlap of our significant regions against published GWAS results for other traits (GWAS catalog; see URLs). Twelve menopause loci were within 1Mb of a previously published genome-wide significant SNP, but most of the co-localised SNPs were in low LD (0 < r<sup>2</sup><0.21) with our SNP in the region (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 7</xref>). The exception was at the <italic>GCKR</italic> locus on chromosome 2. Region 2a (rs2303369) was correlated (r<sup>2</sup> ≈0.5) with four different SNPs reported to influence kidney function, type 2 diabetes, continuous glycaemic traits, as well as serum albumin, C reactive protein, serum urate, and triglycerides. These results increase the observed clustering of signals in complex trait genetics, whilst also adding to the increasing pleiotropy observed at the <italic>GCKR</italic> locus.</p></sec></sec><sec sec-type="discussion" id="S8"><title>Discussion</title><p id="P18">In this large 2-stage GWAS we have confirmed four previously established menopause loci and identified and replicated 13 novel loci associated with age at natural menopause. Of these 17 hits, all but two are intronic or exonic to known genes. On average for associated SNPs in GWAS studies, 40% are intergenic, while only2% of our hits are intergenic. Further, our study finds two times more non-synonymous top hits as typically seen in GWAS (24% vs 12%)<sup><xref rid="R28" ref-type="bibr">28</xref></sup>. The 17 replicated loci function in diverse pathways including hormonal regulation, immune function and DNA repair. Together, they explained 2.5–4.1% of the population variation in menopausal age in independent replication samples. Biological pathway analysis of the genetic associations with age at natural menopause in this study using distinct algorithms and databases were in close agreement in emphasizing general biological pathways for mitochondrial function, DNA repair, cell cycle and cell death, and immune response.</p><p id="P19">Aging is thought to result from the accumulation of somatic damage<sup><xref rid="R29" ref-type="bibr">29</xref></sup>. Analysis of gene expression patterns in aging organs, such as heart and brain, identified changes in genes involved in inflammatory response, oxidative stress, and genome stability<sup><xref rid="R30" ref-type="bibr">30</xref></sup>, processes also identified in analysis of age-related changes in mouse oocytes, including changes in mitochondrial function<sup><xref rid="R31" ref-type="bibr">31</xref></sup>. Comparisons of lifespans across species showed that there is a general relationship between longevity and DNA repair function<sup><xref rid="R32" ref-type="bibr">32</xref></sup>. This notion is reinforced in the Werner and Bloom syndromes, which involve genome instability due to mutations in 3′–5′ DNA helicases of the RecQ family members, and are characterized by both premature aging and premature menopause<sup><xref rid="R33" ref-type="bibr">33</xref></sup>. Similarly, an increase in meiotic errors is associated with an age-related decline in oocyte quality, compounding the progress toward menopause due to follicle depletion<sup><xref rid="R34" ref-type="bibr">34</xref></sup>.</p><p id="P20">In the biological pathways analysis, seven candidate genes identified by proximity to the 17 genome-wide significant associations with age at natural menopause are related to DNA damage repair and replication (<italic>EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG, PRIM1</italic>) (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 4</xref>). The protein encoded by <italic>UIMC1</italic> physically interacts with BRCA1 and estrogen receptor α (ERα) and is thought to recruit BRCA1 to DNA damage sites and to initiate G2/M checkpoint control. PRIM1 (Primase) is involved in DNA replication by synthesising RNA primers for Okazaki fragments during discontinuous replication<sup><xref rid="R35" ref-type="bibr">35</xref></sup>. A mutation in <italic>POLG</italic> can segregate with primary ovarian insufficiency (POI)<sup><xref rid="R36" ref-type="bibr">36</xref></sup>. <italic>Polg</italic> knock-in mice show reduced lifespan, premature ageing, and reduced fertility<sup><xref rid="R37" ref-type="bibr">37</xref></sup>. FANCI, as a second gene at the same locus adjacent to POLG, is a member of the Fanconi anemia (FA) complementation group. FA is a recessive disorder characterized by cytogenetic instability and defective DNA repair. FA patients experience irregular menstruations with menopause occurring around the age of 30<sup><xref rid="R38" ref-type="bibr">38</xref></sup>. The functional polymorphism correlated to our top hit in <italic>EXO1</italic>, has been associated with longevity in female centenarians<sup><xref rid="R39" ref-type="bibr">39</xref></sup>. Male and female <italic>Exo1</italic> knock-out mice are sterile, because the gene is essential for male and female meiosis<sup><xref rid="R40" ref-type="bibr">40</xref></sup>. In addition to the GWAS regions in/near genes previously associated with early menopause, we investigated a panel of candidate genes identified prior to the study, and found a SNP near the meiotic recombination gene <italic>DMC1</italic> to be significantly associated with age at menopause. How the DNA repair pathways contribute to menopause remains unclear. It is possible that with altered DNA repair mechanisms damage accumulates rendering poor quality oocytes for selection. On the other hand, the number of damaged follicles may increase with ageing, resulting in an increased rate of follicle loss through atresia. Next to this, our top hit in this study, one of the four known hits, is a non-synonymous SNP in <italic>MCM8</italic>, was not included in the IPA results, probably because the exact function of this protein is still unknown. The MCM family, however, is a key component of the pre-replication complex and its main function is to restrict DNA replication to one round per cell cycle<sup><xref rid="R41" ref-type="bibr">41</xref></sup>.</p><p id="P21">The pathway analyses highlighted additional candidate genes with functions in DNA repair (exodeoxyribonuclease), but with sub-genome-wide levels of significance for association with age of natural menopause. These 12 candidates (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>) included the Werner (WRN) helicase gene, mutations in which cause Werner syndrome, a classic progeria with advanced ageing phenotype, and ovarian aging<sup><xref rid="R42" ref-type="bibr">42</xref></sup>. Estrogen can enhance WRN expression preventing cell senescence, suggesting its involvement in menopause<sup><xref rid="R43" ref-type="bibr">43</xref></sup>. The identification of DNA repair as one of the biological pathways involved in menopause may also provide an explanation for the association between smoking and an earlier age at menopause. Damage caused by smoking activates several different DNA repair mechanisms. Indeed, a polymorphism in Exo1, one of our top loci, has been associated with colorectal adenomas in smokers only<sup><xref rid="R44" ref-type="bibr">44</xref></sup>. Future studies will reveal whether smoking status modifies the association between age at natural menopause and polymorphisms in DNA repair genes, as has been observed for various cancers.</p><p id="P22">The pathways-based analysis also emphasized that genes related to auto-immune disease also influence age at natural menopause. This link has not been reported before, however, in a proportion (2–10%) of women with POI, ovarian auto-immunity can play a role<sup><xref rid="R45" ref-type="bibr">45</xref></sup>. In addition, POI is frequently associated with additional autoimmune diseases, such as type 1 diabetes mellitus <sup><xref rid="R46" ref-type="bibr">46</xref></sup>. The top SNP in region 19a is near <italic>IL11</italic>, which binds the IL11 receptor alpha chain (IL-11Rα). Female mice with null mutations in <italic>IL-11Rα</italic> are infertile due to defective uterine decidualization, the process necessary for successful embryo implantation<sup><xref rid="R47" ref-type="bibr">47</xref></sup>. <italic>NLRP11</italic> (region 19b) is a member of the <italic>NLRP</italic> family of genes that play important roles in the innate immune system and reproductive system. Several <italic>NLRP</italic> genes show an oocyte specific expression pattern <sup><xref rid="R46" ref-type="bibr">46</xref></sup>, while <italic>NLRP5</italic> has been implicated in POI, and serves as an autoantigen in a mouse model of autoimmune POI<sup><xref rid="R48" ref-type="bibr">48</xref>,<xref rid="R49" ref-type="bibr">49</xref></sup>. Many autoimmune conditions are associated with a particular HLA type, but no such association has been reported for POI<sup><xref rid="R50" ref-type="bibr">50</xref>,<xref rid="R51" ref-type="bibr">51</xref></sup>. One of our top menopause associations (rs1046089) is a missense substitution in <italic>BAT2</italic> (HLA-B associated transcript), which is in the HLA class III complex on chromosome 6 and has been associated with type I diabetes mellitus and rheumatoid arthritis. Multiple phenotypes have been associated with <italic>BAT2</italic> SNPs in GWAS studies including BMI, neonatal lupus, HIV control and height (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 7</xref>), but the SNPs have low correlation with our top hit. Expression data for rs1046089 demonstrated that the polymorphism was associated with altered expression of HLA-DRB4 in monocytes and HLA-DQA1 in lymphoblastoid cell lines (<xref rid="T2" ref-type="table">Table 2</xref>). Thus, this gene is an excellent candidate for a pro-inflammatory component to oocyte depletion affecting menopause age. Indeed, the enrichment of the genes involved in NFκB signalling (<italic>TNF, TNFRSF17, CSNK2B</italic>) in the biological pathways analysis suggests that susceptibility to inflammation, which often accompanies immunosenescence in aging, may also affect ovarian aging. The finding that the innate immune response can be upregulated in response to DNA damage<sup><xref rid="R52" ref-type="bibr">52</xref></sup> suggests that interplay between the two main pathways we have identified (DNA repair and inflammation), may contribute to variation in the age at natural menopause.</p><p id="P23">Three of the 17 regions can be linked to hormonal regulation, an additional route to follicle pool exhaustion. The top region 11 SNP (rs12294104) is in high LD with SNPs in <italic>FSHB</italic> (r<sup>2</sup>=0.92, <xref rid="T2" ref-type="table">Table 2</xref>), a gene which limits the rate of production of follicle stimulating hormone (FSH), a key pituitary expressed hormone that stimulates maturation of follicles. FSH-deficient female mice are infertile<sup><xref rid="R53" ref-type="bibr">53</xref></sup>. Transgenic mice with FSH over-expression show premature infertility due to postimplantation reduction of embryo-fetal survival<sup><xref rid="R54" ref-type="bibr">54</xref></sup>. FSH concentrations rise in women approaching menopause, which might be related to a decrease in growing follicles<sup><xref rid="R55" ref-type="bibr">55</xref></sup>. Mutations in <italic>FSHB</italic> cause hypogonadism and primary amenorrhea in women<sup><xref rid="R56" ref-type="bibr">56</xref></sup> and raised FSH levels and infertility in males<sup><xref rid="R57" ref-type="bibr">57</xref></sup>. The latter observation is due to a promoter polymorphism that may be causal<sup><xref rid="R58" ref-type="bibr">58</xref></sup> and is in LD (r<sup>2</sup> = 0.7) with our most significant SNP. Although <italic>STAR,</italic> encoding steroidogenic acute regulatory protein (StAR) was not the nearest gene to the top SNP in region 8 (rs2517388), its functional role in cleavage of cholesterol to pregnenolone in response to tropic hormones makes it the likely functional candidate, and our top SNP is in high LD with SNPs in that gene (r<sup>2</sup>=0.81, <xref rid="T2" ref-type="table">Table 2</xref>). Pregnenolone is a precursor for several steroid hormones, such as estrogen and progesterone, and mutations in the <italic>StAR</italic> gene are associated with congenital lipoid adrenal hyperplasia and POI<sup><xref rid="R59" ref-type="bibr">59</xref></sup>. Furthermore <italic>STAR</italic> is a target of FOXL2, for which truncating mutations are preferentially associated with POI<sup><xref rid="R60" ref-type="bibr">60</xref></sup>. Similarly, known biological function suggests that <italic>BCAR4</italic>, encoding the breast cancer antiestrogen resistance 4 protein, is the best candidate gene near region 16. <italic>BCAR4</italic> is expressed only in placenta and oocytes and may play a role in hormonal stimulation in the ovary. In breast cancer treatment, tumours expressing higher levels of <italic>BCAR4</italic> are more resistant to tamoxifen treatment<sup><xref rid="R61" ref-type="bibr">61</xref></sup>, reinforcing its role in transduction of hormonal signals.</p><p id="P24">In summary, our findings demonstrate the role of genes which regulate DNA repair and immune function, as well as genes affecting neuroendocrine pathways of ovarian function, indicating the process of ageing as a shared player in both somatic and germ line ageing.</p><p id="P25">We expect a substantial number of additional common variants with small effects on ANM are yet to be identified, and that many of them will be in genes that are in the pathways identified in this study. Sequencing and exome chip studies to determine whether low frequency and rare variants of large effect also contribute to ANM are underway or being planned in many of the cohorts involved in this GWAS. A collaboration of several consortia is currently examining the contribution of common genetic variants to ANM in African American (AA) women, and will allow us to determine whether the genetic variation that affects ANM in AA women are the same or substantially different than for women of primarily European descent. We are currently conducting a study of women with primary ovarian insufficiency to determine whether the variants that are associated with ANM within the normal range also contribute to disease conditions related tothe early menopause phenotype.</p></sec><sec sec-type="methods" id="S9"><title>Methods</title><sec id="S10"><title>Discovery</title><p id="P26">Age at natural menopause was defined as the age at the last menstrual period which occured naturally with at least 12 consecutive months of amenorrhea. This analysis included women with natural menopause between the ages of 40 and 60 years. Women of self-reported non- European ancestry were excluded, as were women with menopause due to hysterectomy and/or bilateral ovariectomy, or chemotherapy/irradiation, if validated by medical records, and women using HRT before menopause. Most cohorts collected the age at natural menopause retrospectively; in the Framingham Offspring, ARIC, NHS and WGHS studies, some women became menopausal under study observation. Study specific questions, mean age at menopause and age at interview are shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 1</xref>. Genotyping and imputation information for the discovery cohorts are shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>. Descriptions of each study are in the <xref rid="SD1" ref-type="supplementary-material">Supplementary Note</xref>.</p></sec><sec id="S11"><title>Replication</title><p id="P27">A total of 14,435 women from 21 studies meeting the same inclusion and exclusion criteria as the discovery analysis women were included in the replication analysis. The women had mean and standard deviation of age at natural menopause similar to the discovery set (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 1</xref>). Genotyping and imputation methods for the <italic>in silico</italic> replication cohorts are shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>. Genotyping information for the studies that genotyped the SNPs <italic>de novo</italic> is shown in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 2</xref>. Descriptions of each study are in the <xref rid="SD1" ref-type="supplementary-material">Supplementary Note</xref>.</p><p id="P28">The 19 independent genome-wide significant SNPs were tested for association with age at natural menopause using linear regression models.</p></sec><sec id="S12"><title>Meta-analysis</title><p id="P29">Inverse variance weighted meta-analysis of the studies was performed using METAL using genomic control<sup><xref rid="R62" ref-type="bibr">62</xref></sup>. A SNP within a study was omitted if the minor allele frequency (MAF) was < 1% or imputation quality score was < 0.2. The discovery meta-analysis included 2,551,160 autosomal SNPs and 38,968 samples.</p></sec><sec id="S13"><title>eQTL analysis</title><p id="P30">For each of the genome-wide significant menopause SNPs (<xref rid="T1" ref-type="table">Table 1</xref>), all proxy SNPs with r<sup>2</sup>>0.8 were determined in HapMap CEU release 22. Each SNP and its proxies were searched against a collected database of expression quantitative trait locus (eQTL) results, including the following tissues: fresh lymphocytes<sup><xref rid="R63" ref-type="bibr">63</xref></sup>, fresh leukocytes<sup><xref rid="R64" ref-type="bibr">64</xref></sup>, leukocyte samples in individuals with Celiac disease<sup><xref rid="R65" ref-type="bibr">65</xref></sup>, lymphoblastoid cell lines (LCL) derived from asthmatic children<sup><xref rid="R66" ref-type="bibr">66</xref></sup>, HapMap LCL from three populations<sup><xref rid="R67" ref-type="bibr">67</xref></sup>, a separate study on HapMap CEU LCL<sup><xref rid="R68" ref-type="bibr">68</xref></sup>, fibroblasts, T cells and LCL derived from cord blood<sup><xref rid="R69" ref-type="bibr">69</xref></sup>, two studies on peripheral blood monocytes<sup><xref rid="R70" ref-type="bibr">70</xref>,<xref rid="R71" ref-type="bibr">71</xref></sup>, CD4+ lymphocytes<sup><xref rid="R72" ref-type="bibr">72</xref></sup>, adipose and blood samples<sup><xref rid="R73" ref-type="bibr">73</xref></sup>, two studies on brain cortex<sup><xref rid="R70" ref-type="bibr">70</xref>,<xref rid="R74" ref-type="bibr">74</xref></sup>, three large studies of brain regions including prefrontal cortex, visual cortex and cerebellum (Emilsson, personal communication), a study of cerebellum, frontal cortex, temporal cortex and caudal pons<sup><xref rid="R75" ref-type="bibr">75</xref></sup>, a separate study on prefrontal cortex<sup><xref rid="R76" ref-type="bibr">76</xref></sup>, liver<sup><xref rid="R77" ref-type="bibr">77</xref></sup>, and osteoblasts<sup><xref rid="R78" ref-type="bibr">78</xref></sup>. The collected eQTL results met criteria for statistical significance for association with gene transcript levels as described in the original papers. <xref rid="T2" ref-type="table">Table 2</xref> provides a summary of eQTL findings for replicated GWAS SNPs.</p></sec><sec id="S14"><title>Conditional analysis</title><p id="P31">On each chromosome, the lowest p-value SNPs that met genome-wide significance were identified. Genome-wide significant SNPs more than 250,000 base pairs and less than 1 million base pairs apart that also had pairwise HapMap CEU linkage disequilibrium values of r<sup>2</sup><0.5 were considered potentially independent regions. Potential independent regions that were within 1 million base pairs of a second region with more significant p-value were tested for independence using conditional analysis. In this analysis, the most significant SNP in the most significant region on each chromosome was used as a covariate in a genome-wide analysis. The second region on the chromosome was then re-tested for independent association.</p></sec><sec id="S15"><title>Pathway analyses</title><p id="P32">Ingenuity pathway analysis (IPA) Knowledge Base 8.8 (see URLs) was used to explore the functional relationship between proteins encoded by the 17 replicated menopause loci. The IPA Knowledge Base contains millions of findings curated from the literature. All reference genes (n=61) within 60kb potentially encoded by the 17 loci (<xref rid="T2" ref-type="table">Table 2</xref>) were entered into the Ingenuity database. Fifty-one genes were eligible for pathway analysis. These eligible ‘focus genes’ were analyzed for direct interactions only. Networks were generated with a maximum size of 35 genes and shown as graphical representations of the molecular relationships between genes or gene products. Proteins are depicted as nodes in various shapes representing the functional class of the protein. Lines depict the biological relationships between nodes. To determine the probability of the analyzed gene to be found together in a network from Ingenuity Pathways Knowledge Base due to random chance alone, IPA applies a Fisher’s exact test. The network score or p<italic>-</italic>value represents the significance of the focus gene enrichment. Enrichment of focus genes to diseases and functional categories was also evaluated in the IPA Knowledge Base. The p<italic>-</italic>value, based on a right-tailed Fisher’s exact test, considers the number of identified focus genes and the total number of molecules known to be associated with these categories in the IPA knowledge database.</p><p id="P33">MAGENTA was used to explore pathway-based associations in the full GWAS dataset. MAGENTA implements a GSEA-based approach, the methodology of which has been previously described<sup><xref rid="R23" ref-type="bibr">23</xref></sup>. Briefly, each gene in the genome is mapped to a single index SNP with the lowest P value within a 110 kb upstream, 40 kb downstream window. This P value, representing a gene score, is then corrected for confounding factors such as gene size, SNP density and LD-related properties in a regression model. Genes within the HLA region were excluded from analysis due to difficulties in accounting for gene density and LD patterns. Each mapped gene in the genome is then ranked by its adjusted gene score. At a given significance threshold (95th and 75th percentiles of all gene scores), the observed number of gene scores in a given pathway, with a ranked score above the specified threshold percentile, is calculated. This observed statistic is then compared to 1,000,000 randomly permuted pathways of identical size. This generates an empirical GSEA P value for each pathway. Significance was determined when an individual pathway reached a false discovery rate < 0.05 in either analysis (<xref rid="SD1" ref-type="supplementary-material">Supplementary Table 5</xref>). In total, 2,580 pathways from Gene Ontology, PANTHER, KEGG and Ingenuity were tested for enrichment of multiple modest associations with age at natural menopause.</p><p id="P34">GRAIL is designed to provide evidence for related biological function among a set of candidate genes. The method is based on connections between gene names and informative words extracted from PubMed abstracts by automated language processing techniques. Genes are considered related, and achieve a high similarity score, if they share informative words. For this analysis, the input for GRAIL was a list of candidate SNPs associated with age at natural menopause. From among candidate genes mapping near the candidate SNPs, GRAIL identifies genes with associated informative words that are significantly similar to informative words from other candidate genes. Genes with significant similarity scores are thus consistent with the set of candidate genes as a whole in having greater sharing of informative words than expected by chance, which may suggest shared biological functions or even biological pathways. GRAIL was first applied to the lead SNPs from each of the replicating genome-wide significant loci using the database of genes and informative words from 2006. Separately, GRAIL was applied to a list of 66 SNPs, one from each locus that had at least one SNP meeting a false discovery rate (FDR) threshold of 0.05 from the QVALUE software in R<sup><xref rid="R79" ref-type="bibr">79</xref></sup>. For the age at natural menopause meta-analysis, the FDR < 0.05 threshold implied a p-value < 2.8×10<sup>−</sup>5.</p></sec><sec id="S16"><title>Candidate gene analysis</title><p id="P35">We explored the association of natural age of menopause with 125 candidate genes selected because of a reported relationship with ovarian function, including animal models where gene mutations affect ovarian function (N=37), human studies of menopause or isolated primary ovarian insufficiency (N=48), syndromes which include ovarian failure (N=4), or genes expressed in the ovary or female germ cells (N=38) (see <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 6</xref>). For each gene, the start and end of transcription was defined by the transcripts that span the largest portion of the genome. NCBI36/hg18 positions taken from the UCSC genome browser were used to define gene and SNP locations. Using the correlation measured from a set of ~850 independent Framingham Heart Study participants, we computed the effective number of independent SNPs for each chromosome <sup><xref rid="R80" ref-type="bibr">80</xref></sup>, and used the total (5,774) in a Bonferroni correction for multiple testing.</p></sec><sec id="S17"><title>Pleiotropy of primary hits</title><p id="P36">Allelic pleiotropy was explored by comparing the genome-wide significant menopause signals to the online catalogue of published genome-wide association studies (GWAS catalog; see URLs). All reported associations that reached P<5×10<sup>−8</sup> and were within 1Mb of the menopause signal were considered. LD estimates between the SNP pairs were assessed using HapMap (CEU, release#27). The results are presented in <xref rid="SD1" ref-type="supplementary-material">Supplementary Table 7</xref>.</p></sec></sec><sec sec-type="supplementary-material" id="S18"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>1</label><media xlink:href="NIHMS342040-supplement-1.pdf" mimetype="application" mime-subtype="pdf" orientation="portrait" xlink:type="simple" id="d37e3155" position="anchor"></media></supplementary-material></sec></body><back><ack id="S19"><p>The authors are very grateful to the study participants and staff from all cohorts involved in this study. Extended acknowledgements per cohort can be found in the <xref rid="SD1" ref-type="supplementary-material">Supplement</xref>.</p></ack><fn-group><fn id="FN4"><p>URLS:</p><p>GWAS catalog: <ext-link ext-link-type="uri" xlink:href="www.genome.gov/gwastudies/">www.genome.gov/gwastudies/</ext-link>,</p><p>SCAN: <ext-link ext-link-type="uri" xlink:href="scan.bsd.uchicago.edu">scan.bsd.uchicago.edu</ext-link>.</p><p>IPA: <ext-link ext-link-type="uri" xlink:href="www.ingenuity.com">www.ingenuity.com</ext-link></p></fn><fn id="FN5" fn-type="financial-disclosure"><p><bold>Financial Disclosures:</bold></p><p>None</p></fn><fn id="FN6" fn-type="con"><p><bold>Author Contributions</bold></p><p>Individual Study design/management: DIC, CHe, EMB, PK, JSB, MBo, EB, HC, SJC, UdF, IJD, GVZD, SE, JGE, LuF, ARF, PG, CJMWvG, CG, DEG, PH, SEH, AH, EI, SLRK, DAL, PKEM, MMar, NGM, VM, NCOM, GPa, ANP, NLP, PHMP, OP, BMP, KR, IR, JMS, RS, VJMP, VG, GE, TBH, LJL, YVS, AT, YTvdS, PMV, GWa, HEW, JFW, BHRW, LL, DIB, JEB, LC, FBH, DJH, GWM, BO, PMR, DS, TDS, KSte, EAS, MU, CMvD, HV, SB, ASa, AMe. Data collection: BZA, SB, LBL, JSB, MBo, AB, HC, PdA, UdF, IJD, GVZD, SE, JGE, LiF, LuF, ARF, DEG, PH, SEH, ACH, AH, ACJWJ, IK, SL, DAL, PKEM, NGM, IMK, ABN, NLP, PHMP, OP, BMP, KR, IR, ASc, SNS, JMS, MGS, US, BT, LT, SU, VJMP, VG, GE, YTvdS, CHvG, JMV, GWa, HEW, AFW, TZ, LZ, MCZ, MZ, LL, AMA, JEB, EAS, AGU, JMM, AMe. Genotyping: JK, LS, TE, EB, FJB, SJC, PdA, GD, PD, CHa, ACH, JLi, BCJMF, SEM, VM, PN, DRN, NCOM, AP, ANP, BMP, JIR, ASi, KSti, AT, KT, YTvdS, MV, EW, TZ, LL, FBH, GWM, BO, UT. Genotype prep: JRBP, MBa, NF, EP, SYS, WVZ, LBL, PdA, GD, CJMWvG, CG, CHa, EI, SLRK, PKEM, IMK, CM, SEM, PN, DRN, NCOM, AP, GPi, ER, CS, JAS, HS, NS, YVS, AT, MV, EW, TZ, LL, FBH, DJH, SS, KLL, MH. Phenotype preparation: JRBP, LS, CHe, MMan, MBa, LB, EMB, FE, NF, DFG, JJH, PK, GZ, WVZ, LBL, MBo, EJCdG, IJD, GVZD, MGS SE, JGE, CHvG, LiF, KF, MH, CHa, EI, ACJWJ, SLRK, IK, JLa, SL, TL, DAL, LML, PKEM, IMK, CM, PHMP, GPi, OP, ER, CS, ASc, JAS, BT, SU, RMvD, VG, GE, TA, YTvdS, HW, GWi, BHRW, AFW, MCZ, LL, AMA, EWD, AMe, KLL, JMM. Analysis plan development: LS, DIC, CHe, EMB, PK, TC, PG, DK, DPK, NGM, DT, DJH, GWM, KLL, JMM, AMu. Analysis plan review: LS, DIC, CHe, AVS, ADC, NG, DK, DPK, BM, ABN, BMP, AMA, DJH, KLL, JMM, AMu. Study Data Analysis: LS, DIC, CHe, MMan, MBa, LB, EMB, FE, TE, NF, DFG, JJH, PK, PFM, EP, SYS, AVS, SvW, GZ, WVZ, EA, CC, MCC, TC, NG, TH, CHa, ZK, JLa, DAL, LML, DM, NCOM, GPa, GPi, ASP, VE, ER, JAS, MGS, SU, YTvdS, MV, LMY, LZ, SS, UT. Reviewed/Interpret analyses: JRBP, LS, DIC, CHe, PS, MBa, EMB, NF, PK, PFM, AVS, BZA, SJC, ADC, IJD, SEH, EI, DK, SLRK, DPK, LML, PKEM, NGM, GPa, ASP, JAS, HS, LMY, JEB, EWD, FBH, DJH, GWM, PMR, CMvD, HV, KLL, JMM, AMu. Meta analyses: LS, PS, KLL. Pathway/other analyses: JRBP, DIC, CHe, ADJ, MMan, GPa, JAV. Meno Study Design: JRBP, LS, DIC, CHe, DEG, PHMP, YTvdS, CHvG, AMe, KLL, JMM, AMu. Manuscript Preparation: JRBP, LS, DIC, CHe, TE, NF, ADC, DK, DPK, EWD, AMe, KLL, JMM, AMu, JAV. Manuscript review: JRBP, LS, DIC, CHe, NF, PK, PFM, AVS, BZA, TA, LBL, JSB, MBo, FJB, HC, SJC, CC, MCC, ADC, GD, UdF, IJD, GE, BCJMF, MEG, NG, DEG, PH, SEH, CHa, EI, DK, DPK, SLRK, JAS, IK, ZK, TL, TE, ASa, AMe, JSEL, JLi, LML, YVL, PKEM, IMK, BM, VM, PN, ABN, NCOM, GPa, ANP, NLP, PHMP, OP, BMP, JIR, IR, HS, JMS, RS, AT, RMvD, YTvdS, CHvG, PMV, MV, GWa, JFW, BHRW, AFW, LMY, TZ, LZ, MCZ, VJMP, LL, AMA, DIB, JEB, EWD, VG, TBH, FBH, DJH, LJL, PMR, TDS, EAS, HV, KLL, JMM, AMu, JAV. 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rules="groups"><thead><tr><th valign="bottom" align="center" rowspan="1" colspan="1">Region number</th><th valign="bottom" align="center" rowspan="1" colspan="1">Most Significant SNP</th><th valign="bottom" align="center" rowspan="1" colspan="1">Chr</th><th valign="bottom" align="center" rowspan="1" colspan="1">Location (bp)</th><th valign="bottom" align="center" rowspan="1" colspan="1">Minor/Major</th><th valign="bottom" align="center" rowspan="1" colspan="1">Analysis</th><th valign="bottom" align="center" rowspan="1" colspan="1">MAF</th><th valign="bottom" align="center" rowspan="1" colspan="1">Effect per minor allele (years)</th><th valign="bottom" align="center" rowspan="1" colspan="1">SE</th><th valign="bottom" align="center" rowspan="1" colspan="1">P</th><th valign="bottom" align="center" rowspan="1" colspan="1">Absolute Effect per minor allele (weeks)</th><th valign="bottom" align="center" rowspan="1" colspan="1">Heterogeneity P-value</th></tr></thead><tbody><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>1a</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs4246511</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="center" valign="top" rowspan="1" colspan="1">39152972</td><td align="center" valign="top" rowspan="1" colspan="1">t/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.271</td><td align="center" valign="top" rowspan="1" colspan="1">0.289</td><td align="center" valign="top" rowspan="1" colspan="1">0.035</td><td align="center" valign="top" rowspan="1" colspan="1">1.02 × 10<sup>−16</sup></td><td align="center" valign="top" rowspan="1" colspan="1">15</td><td align="center" valign="top" rowspan="1" colspan="1">0.288</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.293</td><td align="center" valign="top" rowspan="1" colspan="1">0.133</td><td align="center" valign="top" rowspan="1" colspan="1">0.052</td><td align="center" valign="top" rowspan="1" colspan="1">0.01</td><td align="center" valign="top" rowspan="1" colspan="1">6.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.68</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.24</td><td align="center" valign="top" rowspan="1" colspan="1">0.029</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>9.08</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>17</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">12.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.012</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>1b</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs1635501</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="center" valign="top" rowspan="1" colspan="1">240107398</td><td align="center" valign="top" rowspan="1" colspan="1">c/t</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.478</td><td align="center" valign="top" rowspan="1" colspan="1">−0.188</td><td align="center" valign="top" rowspan="1" colspan="1">0.032</td><td align="center" valign="top" rowspan="1" colspan="1">4.90 × 10<sup>−09</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.08</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.456</td><td align="center" valign="top" rowspan="1" colspan="1">−0.11</td><td align="center" valign="top" rowspan="1" colspan="1">0.048</td><td align="center" valign="top" rowspan="1" colspan="1">0.023</td><td align="center" valign="top" rowspan="1" colspan="1">5.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.016</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.164</td><td align="center" valign="top" rowspan="1" colspan="1">0.027</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>8.46</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>10</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.178</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>2a</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs2303369</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">27568920</td><td align="center" valign="top" rowspan="1" colspan="1">t/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.388</td><td align="center" valign="top" rowspan="1" colspan="1">−0.174</td><td align="center" valign="top" rowspan="1" colspan="1">0.03</td><td align="center" valign="top" rowspan="1" colspan="1">3.80 × 10<sup>−09</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9</td><td align="center" valign="top" rowspan="1" colspan="1">0.639</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.391</td><td align="center" valign="top" rowspan="1" colspan="1">−0.179</td><td align="center" valign="top" rowspan="1" colspan="1">0.047</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>0.000138</italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">9.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.542</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.175</td><td align="center" valign="top" rowspan="1" colspan="1">0.025</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.25</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>12</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">9.1</td><td align="center" valign="top" rowspan="1" colspan="1">0.927</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>2b</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs10183486</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">171699217</td><td align="center" valign="top" rowspan="1" colspan="1">t/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.366</td><td align="center" valign="top" rowspan="1" colspan="1">−0.219</td><td align="center" valign="top" rowspan="1" colspan="1">0.031</td><td align="center" valign="top" rowspan="1" colspan="1">7.88 × 10<sup>−13</sup></td><td align="center" valign="top" rowspan="1" colspan="1">11.4</td><td align="center" valign="top" rowspan="1" colspan="1">0.43</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.362</td><td align="center" valign="top" rowspan="1" colspan="1">−0.141</td><td align="center" valign="top" rowspan="1" colspan="1">0.047</td><td align="center" valign="top" rowspan="1" colspan="1">0.003</td><td align="center" valign="top" rowspan="1" colspan="1">7.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.727</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.196</td><td align="center" valign="top" rowspan="1" colspan="1">0.026</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.21</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>14</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">10.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.169</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>2c</bold><xref rid="TFN2" ref-type="table-fn">a</xref></td><td align="center" valign="top" rowspan="1" colspan="1">rs7606918</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">172603695</td><td align="center" valign="top" rowspan="1" colspan="1">g/a</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.161</td><td align="center" valign="top" rowspan="1" colspan="1">−0.228</td><td align="center" valign="top" rowspan="1" colspan="1">0.041</td><td align="center" valign="top" rowspan="1" colspan="1">2.89 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">11.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.374</td></tr><tr><td colspan="12" align="center" valign="top" rowspan="1">Replication not attempted</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>4</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs4693089</td><td align="center" valign="top" rowspan="1" colspan="1">4</td><td align="center" valign="top" rowspan="1" colspan="1">84592646</td><td align="center" valign="top" rowspan="1" colspan="1">g/a</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.486</td><td align="center" valign="top" rowspan="1" colspan="1">0.209</td><td align="center" valign="top" rowspan="1" colspan="1">0.03</td><td align="center" valign="top" rowspan="1" colspan="1">3.28 × 10<sup>−12</sup></td><td align="center" valign="top" rowspan="1" colspan="1">10.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.336</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.492</td><td align="center" valign="top" rowspan="1" colspan="1">0.273</td><td align="center" valign="top" rowspan="1" colspan="1">0.047</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>6.69</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>09</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">14.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.298</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.228</td><td align="center" valign="top" rowspan="1" colspan="1">0.025</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.38</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>19</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">11.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.254</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>5a</bold><xref rid="TFN3" ref-type="table-fn">b</xref></td><td align="center" valign="top" rowspan="1" colspan="1">rs890835</td><td align="center" valign="top" rowspan="1" colspan="1">5</td><td align="center" valign="top" rowspan="1" colspan="1">175888877</td><td align="center" valign="top" rowspan="1" colspan="1">a/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.112</td><td align="center" valign="top" rowspan="1" colspan="1">0.266</td><td align="center" valign="top" rowspan="1" colspan="1">0.047</td><td align="center" valign="top" rowspan="1" colspan="1">1.17 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">13.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.003</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.115</td><td align="center" valign="top" rowspan="1" colspan="1">−0.037</td><td align="center" valign="top" rowspan="1" colspan="1">0.072</td><td align="center" valign="top" rowspan="1" colspan="1">0.613</td><td align="center" valign="top" rowspan="1" colspan="1">1.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.486</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.177</td><td align="center" valign="top" rowspan="1" colspan="1">0.039</td><td align="center" valign="top" rowspan="1" colspan="1">6.10 × 10<sup>−06</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.0004</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>5b</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs365132</td><td align="center" valign="top" rowspan="1" colspan="1">5</td><td align="center" valign="top" rowspan="1" colspan="1">176311180</td><td align="center" valign="top" rowspan="1" colspan="1">t/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.49</td><td align="center" valign="top" rowspan="1" colspan="1">0.275</td><td align="center" valign="top" rowspan="1" colspan="1">0.029</td><td align="center" valign="top" rowspan="1" colspan="1">1.90 × 10<sup>−21</sup></td><td align="center" valign="top" rowspan="1" colspan="1">14.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.115</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.494</td><td align="center" valign="top" rowspan="1" colspan="1">0.319</td><td align="center" valign="top" rowspan="1" colspan="1">0.046</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>4.26</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>12</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">16.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.728</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.287</td><td align="center" valign="top" rowspan="1" colspan="1">0.025</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>9.11</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>32</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">14.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.416</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>6a</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs2153157</td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">11005474</td><td align="center" valign="top" rowspan="1" colspan="1">a/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.492</td><td align="center" valign="top" rowspan="1" colspan="1">0.184</td><td align="center" valign="top" rowspan="1" colspan="1">0.028</td><td align="center" valign="top" rowspan="1" colspan="1">9.40 × 10<sup>−11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.858</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.116</td><td align="center" valign="top" rowspan="1" colspan="1">0.046</td><td align="center" valign="top" rowspan="1" colspan="1">0.012</td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">0.329</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.165</td><td align="center" valign="top" rowspan="1" colspan="1">0.024</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>7.76</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>12</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.211</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>6b</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs1046089</td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="center" valign="top" rowspan="1" colspan="1">31710946</td><td align="center" valign="top" rowspan="1" colspan="1">a/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.353</td><td align="center" valign="top" rowspan="1" colspan="1">−0.226</td><td align="center" valign="top" rowspan="1" colspan="1">0.031</td><td align="center" valign="top" rowspan="1" colspan="1">1.31 × 10<sup>−13</sup></td><td align="center" valign="top" rowspan="1" colspan="1">11.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.426</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.358</td><td align="center" valign="top" rowspan="1" colspan="1">−0.181</td><td align="center" valign="top" rowspan="1" colspan="1">0.049</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.91</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>04</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">9.4</td><td align="center" valign="top" rowspan="1" colspan="1">0.732</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.213</td><td align="center" valign="top" rowspan="1" colspan="1">0.026</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.63</italic></bold><italic>×</italic><bold><italic>10</italic></bold><italic><sup>−</sup></italic><bold><italic><sup>16</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">11.1</td><td align="center" valign="top" rowspan="1" colspan="1">0.427</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>8</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs2517388</td><td align="center" valign="top" rowspan="1" colspan="1">8</td><td align="center" valign="top" rowspan="1" colspan="1">38096889</td><td align="center" valign="top" rowspan="1" colspan="1">g/t</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.174</td><td align="center" valign="top" rowspan="1" colspan="1">0.274</td><td align="center" valign="top" rowspan="1" colspan="1">0.04</td><td align="center" valign="top" rowspan="1" colspan="1">1.13 × 10<sup>−11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">14.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.67</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.189</td><td align="center" valign="top" rowspan="1" colspan="1">0.234</td><td align="center" valign="top" rowspan="1" colspan="1">0.062</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.52</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>04</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">12.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.708</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.262</td><td align="center" valign="top" rowspan="1" colspan="1">0.034</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>9.31</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>15</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">13.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.591</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>11</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs12294104</td><td align="center" valign="top" rowspan="1" colspan="1">11</td><td align="center" valign="top" rowspan="1" colspan="1">30339475</td><td align="center" valign="top" rowspan="1" colspan="1">t/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.172</td><td align="center" valign="top" rowspan="1" colspan="1">0.226</td><td align="center" valign="top" rowspan="1" colspan="1">0.04</td><td align="center" valign="top" rowspan="1" colspan="1">1.63 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">11.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.721</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.18</td><td align="center" valign="top" rowspan="1" colspan="1">0.223</td><td align="center" valign="top" rowspan="1" colspan="1">0.06</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.18</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>04</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">11.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.239</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.225</td><td align="center" valign="top" rowspan="1" colspan="1">0.033</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.46</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>11</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">11.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.97</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>12</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs2277339</td><td align="center" valign="top" rowspan="1" colspan="1">12</td><td align="center" valign="top" rowspan="1" colspan="1">55432336</td><td align="center" valign="top" rowspan="1" colspan="1">g/t</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.102</td><td align="center" valign="top" rowspan="1" colspan="1">−0.394</td><td align="center" valign="top" rowspan="1" colspan="1">0.051</td><td align="center" valign="top" rowspan="1" colspan="1">5.99 × 10<sup>−15</sup></td><td align="center" valign="top" rowspan="1" colspan="1">20.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.088</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.105</td><td align="center" valign="top" rowspan="1" colspan="1">−0.347</td><td align="center" valign="top" rowspan="1" colspan="1">0.077</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>6.89</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>06</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">18</td><td align="center" valign="top" rowspan="1" colspan="1">0.765</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.38</td><td align="center" valign="top" rowspan="1" colspan="1">0.042</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.47</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>19</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">19.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.61</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>13a</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs3736830</td><td align="center" valign="top" rowspan="1" colspan="1">13</td><td align="center" valign="top" rowspan="1" colspan="1">49204222</td><td align="center" valign="top" rowspan="1" colspan="1">g/c</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.157</td><td align="center" valign="top" rowspan="1" colspan="1">−0.243</td><td align="center" valign="top" rowspan="1" colspan="1">0.04</td><td align="center" valign="top" rowspan="1" colspan="1">1.75 <italic>×</italic> 10<sup>−09</sup></td><td align="center" valign="top" rowspan="1" colspan="1">12.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.859</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.165</td><td align="center" valign="top" rowspan="1" colspan="1">−0.033</td><td align="center" valign="top" rowspan="1" colspan="1">0.062</td><td align="center" valign="top" rowspan="1" colspan="1">0.594</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.905</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.18</td><td align="center" valign="top" rowspan="1" colspan="1">0.034</td><td align="center" valign="top" rowspan="1" colspan="1">9.41 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9.4</td><td align="center" valign="top" rowspan="1" colspan="1">0.005</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>13b</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs4886238</td><td align="center" valign="top" rowspan="1" colspan="1">13</td><td align="center" valign="top" rowspan="1" colspan="1">60011740</td><td align="center" valign="top" rowspan="1" colspan="1">a/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.334</td><td align="center" valign="top" rowspan="1" colspan="1">0.172</td><td align="center" valign="top" rowspan="1" colspan="1">0.031</td><td align="center" valign="top" rowspan="1" colspan="1">3.76 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">8.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.974</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.333</td><td align="center" valign="top" rowspan="1" colspan="1">0.166</td><td align="center" valign="top" rowspan="1" colspan="1">0.049</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>6.09</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>04</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.953</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.17</td><td align="center" valign="top" rowspan="1" colspan="1">0.026</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>9.53</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>11</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.919</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>15</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs2307449</td><td align="center" valign="top" rowspan="1" colspan="1">15</td><td align="center" valign="top" rowspan="1" colspan="1">87664932</td><td align="center" valign="top" rowspan="1" colspan="1">g/t</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.405</td><td align="center" valign="top" rowspan="1" colspan="1">−0.167</td><td align="center" valign="top" rowspan="1" colspan="1">0.03</td><td align="center" valign="top" rowspan="1" colspan="1">2.59 × 10<sup>−08</sup></td><td align="center" valign="top" rowspan="1" colspan="1">8.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.442</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.387</td><td align="center" valign="top" rowspan="1" colspan="1">−0.225</td><td align="center" valign="top" rowspan="1" colspan="1">0.047</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.61</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>06</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">11.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.328</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.184</td><td align="center" valign="top" rowspan="1" colspan="1">0.025</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>3.56</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>13</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">9.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.294</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>16</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs10852344</td><td align="center" valign="top" rowspan="1" colspan="1">16</td><td align="center" valign="top" rowspan="1" colspan="1">11924420</td><td align="center" valign="top" rowspan="1" colspan="1">c/t</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.415</td><td align="center" valign="top" rowspan="1" colspan="1">0.198</td><td align="center" valign="top" rowspan="1" colspan="1">0.029</td><td align="center" valign="top" rowspan="1" colspan="1">1.28 × 10<sup>−11</sup></td><td align="center" valign="top" rowspan="1" colspan="1">10.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.014</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.426</td><td align="center" valign="top" rowspan="1" colspan="1">0.093</td><td align="center" valign="top" rowspan="1" colspan="1">0.046</td><td align="center" valign="top" rowspan="1" colspan="1">0.042</td><td align="center" valign="top" rowspan="1" colspan="1">4.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.599</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.168</td><td align="center" valign="top" rowspan="1" colspan="1">0.025</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.01</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>11</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.054</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>19a</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs11668344</td><td align="center" valign="top" rowspan="1" colspan="1">19</td><td align="center" valign="top" rowspan="1" colspan="1">60525476</td><td align="center" valign="top" rowspan="1" colspan="1">g/a</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.363</td><td align="center" valign="top" rowspan="1" colspan="1">−0.416</td><td align="center" valign="top" rowspan="1" colspan="1">0.03</td><td align="center" valign="top" rowspan="1" colspan="1">5.94 × 10<sup>−43</sup></td><td align="center" valign="top" rowspan="1" colspan="1">21.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.112</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.36</td><td align="center" valign="top" rowspan="1" colspan="1">−0.415</td><td align="center" valign="top" rowspan="1" colspan="1">0.048</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>2.65</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>18</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">21.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.517</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.416</td><td align="center" valign="top" rowspan="1" colspan="1">0.026</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.45</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>59</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">21.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.987</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>19b</bold><xref rid="TFN4" ref-type="table-fn">c</xref></td><td align="center" valign="top" rowspan="1" colspan="1">rs12461110</td><td align="center" valign="top" rowspan="1" colspan="1">19</td><td align="center" valign="top" rowspan="1" colspan="1">61012475</td><td align="center" valign="top" rowspan="1" colspan="1">a/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.356</td><td align="center" valign="top" rowspan="1" colspan="1">−0.174</td><td align="center" valign="top" rowspan="1" colspan="1">0.03</td><td align="center" valign="top" rowspan="1" colspan="1">9.49 × 10<sup>−09</sup></td><td align="center" valign="top" rowspan="1" colspan="1">9.1</td><td align="center" valign="top" rowspan="1" colspan="1">0.835</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.344</td><td align="center" valign="top" rowspan="1" colspan="1">−0.117</td><td align="center" valign="top" rowspan="1" colspan="1">0.049</td><td align="center" valign="top" rowspan="1" colspan="1">0.018</td><td align="center" valign="top" rowspan="1" colspan="1">6.1</td><td align="center" valign="top" rowspan="1" colspan="1">0.542</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">−0.158</td><td align="center" valign="top" rowspan="1" colspan="1">0.026</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>8.74</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>10</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">8.2</td><td align="center" valign="top" rowspan="1" colspan="1">0.32</td></tr><tr><td colspan="12" valign="bottom" align="left" rowspan="1"><hr></hr></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"><bold>20</bold></td><td align="center" valign="top" rowspan="1" colspan="1">rs16991615</td><td align="center" valign="top" rowspan="1" colspan="1">20</td><td align="center" valign="top" rowspan="1" colspan="1">5896227</td><td align="center" valign="top" rowspan="1" colspan="1">a/g</td><td align="center" valign="top" rowspan="1" colspan="1">Discovery</td><td align="center" valign="top" rowspan="1" colspan="1">0.069</td><td align="center" valign="top" rowspan="1" colspan="1">0.971</td><td align="center" valign="top" rowspan="1" colspan="1">0.062</td><td align="center" valign="top" rowspan="1" colspan="1">1.16 × 10<sup>−54</sup></td><td align="center" valign="top" rowspan="1" colspan="1">50.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.356</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Replication</td><td align="center" valign="top" rowspan="1" colspan="1">0.07</td><td align="center" valign="top" rowspan="1" colspan="1">0.896</td><td align="center" valign="top" rowspan="1" colspan="1">0.096</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>7.90</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>21</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">46.6</td><td align="center" valign="top" rowspan="1" colspan="1">0.088</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">Combined</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">0.948</td><td align="center" valign="top" rowspan="1" colspan="1">0.052</td><td align="center" valign="top" rowspan="1" colspan="1"><bold><italic>1.42</italic></bold><italic>×</italic><bold><italic>10</italic></bold><sup>−</sup><bold><italic><sup>73</sup></italic></bold></td><td align="center" valign="top" rowspan="1" colspan="1">49.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.509</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>MAF: minor allele frequency; Heterogeneity: p-values for heterogeneity among discovery studies, replication studies, and comparing all discovery to all replication studies. P- value: Replication p-values that meet the criterion P<0.05/19 are indicated in bold italics. Combined analysis p-values that reached genome-wide significance are indicated in bold italics.</p></fn><fn id="TFN2"><label>a</label><p>Conditional analysis: beta(SE): −0.199(0.041); p-value:9.8 × 10<sup>−07</sup></p></fn><fn id="TFN3"><label>b</label><p>Conditional analysis beta(SE): 0.267(0.046); p-value:6.5 × 10<sup>−09</sup></p></fn><fn id="TFN4"><label>c</label><p>Conditional analysis: beta(SE): −0.168(0.031); p-value:3.8 × 10<sup>−08</sup></p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><p>Characteristics of the top SNP in each region.</p></caption><table frame="below" rules="groups"><thead><tr><th valign="bottom" align="center" rowspan="1" colspan="1">Region</th><th valign="bottom" align="center" rowspan="1" colspan="1">SNPID</th><th valign="bottom" align="center" rowspan="1" colspan="1">Chr</th><th valign="bottom" align="right" rowspan="1" colspan="1">Location (bp)</th><th valign="bottom" align="center" rowspan="1" colspan="1">gene</th><th valign="bottom" align="center" rowspan="1" colspan="1">feature</th><th valign="bottom" align="left" rowspan="1" colspan="1">Other refgenes<60kb from SNP</th><th valign="bottom" align="left" rowspan="1" colspan="1">Genes with SNPs in LD (r<sup>2</sup>>0.5) with SNP (gene:r<sup>2</sup>)</th><th valign="bottom" align="left" rowspan="1" colspan="1">eQTL</th></tr></thead><tbody><tr><td align="center" valign="top" rowspan="1" colspan="1">1a</td><td align="center" valign="top" rowspan="1" colspan="1">rs4246511</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="right" valign="top" rowspan="1" colspan="1">39,152,972</td><td align="center" valign="top" rowspan="1" colspan="1">RHBDL2</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">MYCBP;GJA10;RRAGC</td><td align="left" valign="top" rowspan="1" colspan="1">MYCBP:0.678; RHBDL2:0.678; RRAGC:0.678; GJA9:0.678; LOC100130627:0.678</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">1b</td><td align="center" valign="top" rowspan="1" colspan="1">rs1635501</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="right" valign="top" rowspan="1" colspan="1">240,107,398</td><td align="center" valign="top" rowspan="1" colspan="1">EXO1</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">LOC100131576:0.678; WDR64:0.923; LOC100133057:1; EXO1:1</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">2a</td><td align="center" valign="top" rowspan="1" colspan="1">rs2303369</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="right" valign="top" rowspan="1" colspan="1">27,568,920</td><td align="center" valign="top" rowspan="1" colspan="1">FNDC4</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">GCKR;KRTCAP3;IFT172;N RBP1</td><td align="left" valign="top" rowspan="1" colspan="1">FTHL3P:0.967; GCKR:1; GTF3C2:0.967; MPV17:0.967; PPM1G:0.967; UCN:0.841; EIF2B4:0.967; SNX17:0.967; IFT172:1; NRBP1:0.967; TRIM54:0.841; FNDC4:1; C2orf16:0.513; ZNF513:0.967; KRTCAP3:1; DNAJC5G:0.841; LOC100130981:0.901</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.9 with multiple eSNPs for IFT172n lymph, adipose, and blood; r2>0.9 with multiple eSNPs for KRTCAP3 in lymph and CD4; r2>0.9 with eSNP for SNX17 in PFC</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">2b</td><td align="center" valign="top" rowspan="1" colspan="1">rs10183486</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="right" valign="top" rowspan="1" colspan="1">171,699,217</td><td align="center" valign="top" rowspan="1" colspan="1">TLK1</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">GORASP2:0.929; TLK1:0.964</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.9 with eSNPs for TLK1 in LCL and PFC</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">4</td><td align="center" valign="top" rowspan="1" colspan="1">rs4693089</td><td align="center" valign="top" rowspan="1" colspan="1">4</td><td align="right" valign="top" rowspan="1" colspan="1">84,592,646</td><td align="center" valign="top" rowspan="1" colspan="1">HELQ</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">MRPS18C;FAM175A</td><td align="left" valign="top" rowspan="1" colspan="1">MRPS18C:1; FAM175A:1; AGPAT9:1; HEL308:1; OK/SW-CL.36:1</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.80 with eSNPs for MRPS18C in Lymph and PFC; r<sup>2</sup>>0.80 for AGPAT9 in Fibroblast</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">5a</td><td align="center" valign="top" rowspan="1" colspan="1">rs890835</td><td align="center" valign="top" rowspan="1" colspan="1">5</td><td align="right" valign="top" rowspan="1" colspan="1">175,888,877</td><td align="center" valign="top" rowspan="1" colspan="1">RNF44</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">UBXD8;PCLKC</td><td align="left" valign="top" rowspan="1" colspan="1">SNCB:0.318; RNF44:1; FAF2:1; PCDH24:1</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">5b</td><td align="center" valign="top" rowspan="1" colspan="1">rs365132</td><td align="center" valign="top" rowspan="1" colspan="1">5</td><td align="right" valign="top" rowspan="1" colspan="1">176,311,180</td><td align="center" valign="top" rowspan="1" colspan="1">UIMC1</td><td align="center" valign="top" rowspan="1" colspan="1">coding-synonymous</td><td align="left" valign="top" rowspan="1" colspan="1">HK3</td><td align="left" valign="top" rowspan="1" colspan="1">FGFR4:0.871; HK3:0.967; ZNF346:0.966; UIMC1:0.967; UNC5A:0.932</td><td align="left" valign="top" rowspan="1" colspan="1">eSNP for Hs.484258 in Lymph; for FGFR4 and ZNF346 in PFC; for ZNF346 in VC</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">6a</td><td align="center" valign="top" rowspan="1" colspan="1">rs2153157</td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="right" valign="top" rowspan="1" colspan="1">11,005,474</td><td align="center" valign="top" rowspan="1" colspan="1">SYCP2L</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">GCM2</td><td align="left" valign="top" rowspan="1" colspan="1">MAK:0.602; GCM2:0.602; SYCP2L:0.602</td><td align="left" valign="top" rowspan="1" colspan="1">eSNP for SYCP2L in monocytes</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">6b</td><td align="center" valign="top" rowspan="1" colspan="1">rs1046089<xref rid="TFN5" ref-type="table-fn">a</xref></td><td align="center" valign="top" rowspan="1" colspan="1">6</td><td align="right" valign="top" rowspan="1" colspan="1">31,710,946</td><td align="center" valign="top" rowspan="1" colspan="1">BAT2</td><td align="center" valign="top" rowspan="1" colspan="1">missense</td><td align="left" valign="top" rowspan="1" colspan="1">BAT3;LST1;C6orf47;APOM; AIF1; NCR3; LY6G5C;LTB;BAT5;CSNK2 B;LY6G5B;BAT4;TNF</td><td align="left" valign="top" rowspan="1" colspan="1">AIF1:0.963; CLIC1:0.682; CSNK2B:0.963; HSPA1A:0.649; HSPA1B:0.587; HSPA1L:0.649; LTB:0.963; MSH5:0.682; NEU1:0.587; VARS:0.682; BAT2:0.963; BAT3:0.963; BAT4:0.963; BAT5:0.963; LST1:0.963; DDAH2:0.682; SNORD52:0.587; SNORD48:0.587; C6orf48:0.587; APOM:0.963; LSM2:0.649; C6orf47:0.963; LY6G5B:0.963; LY6G6D:0.963; LY6G6E:0.963; SLC44A4:0.587; C6orf27:0.682; C6orf25:0.682; LY6G6C:0.961; LY6G5C:0.963; NCR3:0.963; LY6G6F:0.963; C6orf26:0.682; SNORA38:0.963; LOC100130756:0.963</td><td align="left" valign="top" rowspan="1" colspan="1">eSNP for LY6G5C in CD4 and Lymph; for HLA-DRB4 in monocytes; for C6orf10 in VC; for AIF1 in Lymph; for HLA-DQA1 in LCL</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">8</td><td align="center" valign="top" rowspan="1" colspan="1">rs2517388</td><td align="center" valign="top" rowspan="1" colspan="1">8</td><td align="right" valign="top" rowspan="1" colspan="1">38,096,889</td><td align="center" valign="top" rowspan="1" colspan="1">ASH2L</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">BAG4;EIF4EBP1;LSM1;ST AR</td><td align="left" valign="top" rowspan="1" colspan="1">STAR:0.831; ASH2L:0.831; LSM1:0.831</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">11</td><td align="center" valign="top" rowspan="1" colspan="1">rs12294104</td><td align="center" valign="top" rowspan="1" colspan="1">11</td><td align="right" valign="top" rowspan="1" colspan="1">30,339,475</td><td align="center" valign="top" rowspan="1" colspan="1">--</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">MPPED2;C11orf46</td><td align="left" valign="top" rowspan="1" colspan="1">FSHB:0.92; C11orf46:1</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.9 with eSNP for C11orf46 in Lymph</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">12</td><td align="center" valign="top" rowspan="1" colspan="1">rs2277339<xref rid="TFN6" ref-type="table-fn">b</xref></td><td align="center" valign="top" rowspan="1" colspan="1">12</td><td align="right" valign="top" rowspan="1" colspan="1">55,432,336</td><td align="center" valign="top" rowspan="1" colspan="1">PRIM1</td><td align="center" valign="top" rowspan="1" colspan="1">missense</td><td align="left" valign="top" rowspan="1" colspan="1">HSD17B6;NACA</td><td align="left" valign="top" rowspan="1" colspan="1">-</td><td align="left" valign="top" rowspan="1" colspan="1">eSNP for PRIM1 in VC, CR, PFC</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">13a</td><td align="center" valign="top" rowspan="1" colspan="1">rs3736830</td><td align="center" valign="top" rowspan="1" colspan="1">13</td><td align="right" valign="top" rowspan="1" colspan="1">49,204,222</td><td align="center" valign="top" rowspan="1" colspan="1">KPNA3</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">EBPL</td><td align="left" valign="top" rowspan="1" colspan="1">KPNA3:0.734; EBPL:0.734; ARL11:0.623; LOC100131941:0.623</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">13b</td><td align="center" valign="top" rowspan="1" colspan="1">rs4886238</td><td align="center" valign="top" rowspan="1" colspan="1">13</td><td align="right" valign="top" rowspan="1" colspan="1">60,011,740</td><td align="center" valign="top" rowspan="1" colspan="1">TDRD3</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">TDRD3:1; LOC390407:0.731</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.8 with eSNP in Adipose for TDRD3</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">15</td><td align="center" valign="top" rowspan="1" colspan="1">rs2307449</td><td align="center" valign="top" rowspan="1" colspan="1">15</td><td align="right" valign="top" rowspan="1" colspan="1">87,664,932</td><td align="center" valign="top" rowspan="1" colspan="1">POLG</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">FANCI</td><td align="left" valign="top" rowspan="1" colspan="1">POLG:0.965; RLBP1:0.898; ABHD2:0.898; FANCI:0.965; LOC728003:0.898; LOC100131654:0.683</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.8 with eSNP for RLBP1 in PFC</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">16</td><td align="center" valign="top" rowspan="1" colspan="1">rs10852344</td><td align="center" valign="top" rowspan="1" colspan="1">16</td><td align="right" valign="top" rowspan="1" colspan="1">11,924,420</td><td align="center" valign="top" rowspan="1" colspan="1">--</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">TNFRSF17;RUNDC2A;GSP T1</td><td align="left" valign="top" rowspan="1" colspan="1">TNFRSF17:0.662; GSPT1:1; COX6CP1:1; RSL1D1:1; ZC3H7A:0.701; RUNDC2A:0.662; LOC729978:1</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">19a</td><td align="center" valign="top" rowspan="1" colspan="1">rs11668344</td><td align="center" valign="top" rowspan="1" colspan="1">19</td><td align="right" valign="top" rowspan="1" colspan="1">60,525,476</td><td align="center" valign="top" rowspan="1" colspan="1">TMEM150B</td><td align="center" valign="top" rowspan="1" colspan="1">intron</td><td align="left" valign="top" rowspan="1" colspan="1">BRSK1;HSPBP1;COX6B2;L OC284417;IL11; SUV420H2</td><td align="left" valign="top" rowspan="1" colspan="1">IL11:0.962; SAPS1:0.894; HSPBP1:0.962; BRSK1:0.962; SUV420H2:0.962; COX6B2:0.962; LOC284417:0.962; FAM71E2:0.962</td><td align="left" valign="top" rowspan="1" colspan="1">r<sup>2</sup>>0.8 with eSNP for MGC2705 in adipose and blood</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">19b</td><td align="center" valign="top" rowspan="1" colspan="1">rs12461110<xref rid="TFN7" ref-type="table-fn">c</xref></td><td align="center" valign="top" rowspan="1" colspan="1">19</td><td align="right" valign="top" rowspan="1" colspan="1">61,012,475</td><td align="center" valign="top" rowspan="1" colspan="1">NLRP11</td><td align="center" valign="top" rowspan="1" colspan="1">missense</td><td align="left" valign="top" rowspan="1" colspan="1">NLRP4</td><td align="left" valign="top" rowspan="1" colspan="1">NLRP4:0.514; NLRP11:0.514; RFPL4A:0.514; LOC646663:0.514; LOC729974:0.514</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">20</td><td align="center" valign="top" rowspan="1" colspan="1">rs16991615<xref rid="TFN8" ref-type="table-fn">d</xref></td><td align="center" valign="top" rowspan="1" colspan="1">20</td><td align="right" valign="top" rowspan="1" colspan="1">5,896,227</td><td align="center" valign="top" rowspan="1" colspan="1">MCM8</td><td align="center" valign="top" rowspan="1" colspan="1">missense</td><td align="left" valign="top" rowspan="1" colspan="1">CRLS1;CHGB;TRMT6</td><td align="left" valign="top" rowspan="1" colspan="1">-</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="TFN5"><label>a</label><p>Arg > His; Predicted to be Damaging (SIFT), Benign (Polyphen2)</p></fn><fn id="TFN6"><label>b</label><p>Asp > Ala; Predicted to be Damaging (SIFT), Probably damaging (Polyphen2)</p></fn><fn id="TFN7"><label>c</label><p>Pro > Leu; Predicted to be Damaging (SIFT), Benign (Polyphen2)</p></fn><fn id="TFN8"><label>d</label><p>Glu > Lys; Predicted to be Tolerated (SIFT), Benign (Polyphen2)</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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