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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function</title><author><name sortKey="Pattaro, Cristian" sort="Pattaro, Cristian" uniqKey="Pattaro C" first="Cristian" last="Pattaro">Cristian Pattaro</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kottgen, Anna" sort="Kottgen, Anna" uniqKey="Kottgen A" first="Anna" last="Köttgen">Anna Köttgen</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Teumer, Alexander" sort="Teumer, Alexander" uniqKey="Teumer A" first="Alexander" last="Teumer">Alexander Teumer</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Garnaas, Maija" sort="Garnaas, Maija" uniqKey="Garnaas M" first="Maija" last="Garnaas">Maija Garnaas</name><affiliation><nlm:aff id="aff5"><addr-line>Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Boger, Carsten A" sort="Boger, Carsten A" uniqKey="Boger C" first="Carsten A." last="Böger">Carsten A. Böger</name><affiliation><nlm:aff id="aff6"><addr-line>Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fuchsberger, Christian" sort="Fuchsberger, Christian" uniqKey="Fuchsberger C" first="Christian" last="Fuchsberger">Christian Fuchsberger</name><affiliation><nlm:aff id="aff7"><addr-line>Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Olden, Matthias" sort="Olden, Matthias" uniqKey="Olden M" first="Matthias" last="Olden">Matthias Olden</name><affiliation><nlm:aff id="aff8"><addr-line>Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><addr-line>Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chen, Ming Huei" sort="Chen, Ming Huei" uniqKey="Chen M" first="Ming-Huei" last="Chen">Ming-Huei Chen</name><affiliation><nlm:aff id="aff10"><addr-line>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tin, Adrienne" sort="Tin, Adrienne" uniqKey="Tin A" first="Adrienne" last="Tin">Adrienne Tin</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Taliun, Daniel" sort="Taliun, Daniel" uniqKey="Taliun D" first="Daniel" last="Taliun">Daniel Taliun</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gao, Xiaoyi" sort="Gao, Xiaoyi" uniqKey="Gao X" first="Xiaoyi" last="Gao">Xiaoyi Gao</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gorski, Mathias" sort="Gorski, Mathias" uniqKey="Gorski M" first="Mathias" last="Gorski">Mathias Gorski</name><affiliation><nlm:aff id="aff13"><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="aff15"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hundertmark, Claudia" sort="Hundertmark, Claudia" uniqKey="Hundertmark C" first="Claudia" last="Hundertmark">Claudia Hundertmark</name><affiliation><nlm:aff id="aff16"><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Foster, Meredith C" sort="Foster, Meredith C" uniqKey="Foster M" first="Meredith C." last="Foster">Meredith C. Foster</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="O Seaghdha, Conall M" sort="O Seaghdha, Conall M" uniqKey="O Seaghdha C" first="Conall M." last="O'Seaghdha">Conall M. O'Seaghdha</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff18"><addr-line>Division of Nephrology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></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="aff19"><addr-line>Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Isaacs, Aaron" sort="Isaacs, Aaron" uniqKey="Isaacs A" first="Aaron" last="Isaacs">Aaron Isaacs</name><affiliation><nlm:aff id="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff21"><addr-line>Centre for Medical Systems Biology, Leiden, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="aff22"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="O Connell, Jeffrey R" sort="O Connell, Jeffrey R" uniqKey="O Connell J" first="Jeffrey R." last="O'Connell">Jeffrey R. O'Connell</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Struchalin, Maksim" sort="Struchalin, Maksim" uniqKey="Struchalin M" first="Maksim" last="Struchalin">Maksim Struchalin</name><affiliation><nlm:aff id="aff26"><addr-line>Department of Epidemiology and Biostatistics and Department of Forensic Molecular Biology, Erasmus University Medical Centre, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tanaka, Toshiko" sort="Tanaka, Toshiko" uniqKey="Tanaka T" first="Toshiko" last="Tanaka">Toshiko Tanaka</name><affiliation><nlm:aff id="aff27"><addr-line>Clinical Research Branch, National Institute of Aging, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Guo" sort="Li, Guo" uniqKey="Li G" first="Guo" last="Li">Guo Li</name><affiliation><nlm:aff id="aff28"><addr-line>University of Washington, Seattle, Washington, United States of America</addr-line></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="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gierman, Hinco J" sort="Gierman, Hinco J" uniqKey="Gierman H" first="Hinco J." last="Gierman">Hinco J. Gierman</name><affiliation><nlm:aff id="aff29"><addr-line>Department of Developmental Biology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Feitosa, Mary" sort="Feitosa, Mary" uniqKey="Feitosa M" first="Mary" last="Feitosa">Mary Feitosa</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Atkinson, Elizabeth J" sort="Atkinson, Elizabeth J" uniqKey="Atkinson E" first="Elizabeth J." last="Atkinson">Elizabeth J. Atkinson</name><affiliation><nlm:aff id="aff30"><addr-line>Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="aff31"><addr-line>Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></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="aff32"><addr-line>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Johansson, Sa" sort="Johansson, Sa" uniqKey="Johansson " first=" Sa" last="Johansson"> Sa Johansson</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tonjes, Anke" sort="Tonjes, Anke" uniqKey="Tonjes A" first="Anke" last="Tönjes">Anke Tönjes</name><affiliation><nlm:aff id="aff34"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff35"><addr-line>IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chouraki, Vincent" sort="Chouraki, Vincent" uniqKey="Chouraki V" first="Vincent" last="Chouraki">Vincent Chouraki</name><affiliation><nlm:aff id="aff37"><addr-line>Inserm UMR744, Institut Pasteur, Lille, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G." last="Holliday">Elizabeth G. Holliday</name><affiliation><nlm:aff id="aff38"><addr-line>Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, Australia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff39"><addr-line>Centre for Information-based Medicine, Hunter Medical Research Institute, Newcastle, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Sorice, Rossella" sort="Sorice, Rossella" uniqKey="Sorice R" first="Rossella" last="Sorice">Rossella Sorice</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltan" last="Kutalik">Zoltan Kutalik</name><affiliation><nlm:aff id="aff41"><addr-line>Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff42"><addr-line>Swiss Institute of Bioinformatics, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="aff43"><addr-line>Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Centre for Laboratory Medicine Tampere Finn-Medi 2, Tampere, Finland</addr-line></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="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Deshmukh, Harshal" sort="Deshmukh, Harshal" uniqKey="Deshmukh H" first="Harshal" last="Deshmukh">Harshal Deshmukh</name><affiliation><nlm:aff id="aff46"><addr-line>Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></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="aff47"><addr-line>Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chu, Audrey Y" sort="Chu, Audrey Y" uniqKey="Chu A" first="Audrey Y." last="Chu">Audrey Y. Chu</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Murgia, Federico" sort="Murgia, Federico" uniqKey="Murgia F" first="Federico" last="Murgia">Federico Murgia</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="aff50"><addr-line>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Imboden, Medea" sort="Imboden, Medea" uniqKey="Imboden M" first="Medea" last="Imboden">Medea Imboden</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kollerits, Barbara" sort="Kollerits, Barbara" uniqKey="Kollerits B" first="Barbara" last="Kollerits">Barbara Kollerits</name><affiliation><nlm:aff id="aff52"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></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="aff54"><addr-line>Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland, United States of America</addr-line></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="aff54"><addr-line>Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland, United States of America</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></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="aff55"><addr-line>Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name><affiliation><nlm:aff id="aff56"><addr-line>Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry and Department of Neurology, Medical University Graz, Graz, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Cavalieri, Margherita" sort="Cavalieri, Margherita" uniqKey="Cavalieri M" first="Margherita" last="Cavalieri">Margherita Cavalieri</name><affiliation><nlm:aff id="aff57"><addr-line>Austrian Stroke Prevention Study, University Clinic of Neurology, Department of Special Neurology, Medical University Graz, Graz, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rao, Madhumathi" sort="Rao, Madhumathi" uniqKey="Rao M" first="Madhumathi" last="Rao">Madhumathi Rao</name><affiliation><nlm:aff id="aff58"><addr-line>Division of Nephrology/Tufts Evidence Practice Center, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America</addr-line></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="aff32"><addr-line>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Demirkan, Ayse" sort="Demirkan, Ayse" uniqKey="Demirkan A" first="Ayse" last="Demirkan">Ayse Demirkan</name><affiliation><nlm:aff id="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="De Andrade, Mariza" sort="De Andrade, Mariza" uniqKey="De Andrade M" first="Mariza" last="De Andrade">Mariza De Andrade</name><affiliation><nlm:aff id="aff30"><addr-line>Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Turner, Stephen T" sort="Turner, Stephen T" uniqKey="Turner S" first="Stephen T." last="Turner">Stephen T. Turner</name><affiliation><nlm:aff id="aff59"><addr-line>Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ding, Jingzhong" sort="Ding, Jingzhong" uniqKey="Ding J" first="Jingzhong" last="Ding">Jingzhong Ding</name><affiliation><nlm:aff id="aff60"><addr-line>Department of Internal Medicine/Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Andrews, Jeanette S" sort="Andrews, Jeanette S" uniqKey="Andrews J" first="Jeanette S." last="Andrews">Jeanette S. Andrews</name><affiliation><nlm:aff id="aff61"><addr-line>Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Freedman, Barry I" sort="Freedman, Barry I" uniqKey="Freedman B" first="Barry I." last="Freedman">Barry I. Freedman</name><affiliation><nlm:aff id="aff62"><addr-line>Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Koenig, Wolfgang" sort="Koenig, Wolfgang" uniqKey="Koenig W" first="Wolfgang" last="Koenig">Wolfgang Koenig</name><affiliation><nlm:aff id="aff63"><addr-line>Abteilung Innere II, Universitätsklinikum Ulm, Ulm, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation><nlm:aff id="aff64"><addr-line>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Doring, Angela" sort="Doring, Angela" uniqKey="Doring A" first="Angela" last="Döring">Angela Döring</name><affiliation><nlm:aff id="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff64"><addr-line>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></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="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff65"><addr-line>Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff66"><addr-line>Klinikum Grosshadern, Neuherberg, Germany</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Minelli, Cosetta" sort="Minelli, Cosetta" uniqKey="Minelli C" first="Cosetta" last="Minelli">Cosetta Minelli</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wheeler, Heather E" sort="Wheeler, Heather E" uniqKey="Wheeler H" first="Heather E." last="Wheeler">Heather E. Wheeler</name><affiliation><nlm:aff id="aff68"><addr-line>Department of Genetics, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff69"><addr-line>Department of Medicine, University of Chicago, Chicago, Illinois, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Igl, Wilmar" sort="Igl, Wilmar" uniqKey="Igl W" first="Wilmar" last="Igl">Wilmar Igl</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Zaboli, Ghazal" sort="Zaboli, Ghazal" uniqKey="Zaboli G" first="Ghazal" last="Zaboli">Ghazal Zaboli</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wild, Sarah H" sort="Wild, Sarah H" uniqKey="Wild S" first="Sarah H." last="Wild">Sarah H. Wild</name><affiliation><nlm:aff id="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></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="aff71"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ellinghaus, David" sort="Ellinghaus, David" uniqKey="Ellinghaus D" first="David" last="Ellinghaus">David Ellinghaus</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nothlings, Ute" sort="Nothlings, Ute" uniqKey="Nothlings U" first="Ute" last="Nöthlings">Ute Nöthlings</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff73"><addr-line>popgen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jacobs, Gunnar" sort="Jacobs, Gunnar" uniqKey="Jacobs G" first="Gunnar" last="Jacobs">Gunnar Jacobs</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff73"><addr-line>popgen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Biffar, Reiner" sort="Biffar, Reiner" uniqKey="Biffar R" first="Reiner" last="Biffar">Reiner Biffar</name><affiliation><nlm:aff id="aff74"><addr-line>Clinic for Prosthodontic Dentistry, Gerostomatology, and Material Science, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Endlich, Karlhans" sort="Endlich, Karlhans" uniqKey="Endlich K" first="Karlhans" last="Endlich">Karlhans Endlich</name><affiliation><nlm:aff id="aff75"><addr-line>Institute of Anatomy and Cell Biology, University of Greifswald, Greifswald, Germany</addr-line></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="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kroemer, Heyo K" sort="Kroemer, Heyo K" uniqKey="Kroemer H" first="Heyo K." last="Kroemer">Heyo K. Kroemer</name><affiliation><nlm:aff id="aff76"><addr-line>Institute of Pharmacology, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nauck, Matthias" sort="Nauck, Matthias" uniqKey="Nauck M" first="Matthias" last="Nauck">Matthias Nauck</name><affiliation><nlm:aff id="aff77"><addr-line>Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stracke, Sylvia" sort="Stracke, Sylvia" uniqKey="Stracke S" first="Sylvia" last="Stracke">Sylvia Stracke</name><affiliation><nlm:aff id="aff78"><addr-line>Clinic for Internal Medicine A, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Volker, Uwe" sort="Volker, Uwe" uniqKey="Volker U" first="Uwe" last="Völker">Uwe Völker</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></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="aff79"><addr-line>Institute for Community Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kovacs, Peter" sort="Kovacs, Peter" uniqKey="Kovacs P" first="Peter" last="Kovacs">Peter Kovacs</name><affiliation><nlm:aff id="aff80"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stumvoll, Michael" sort="Stumvoll, Michael" uniqKey="Stumvoll M" first="Michael" last="Stumvoll">Michael Stumvoll</name><affiliation><nlm:aff id="aff34"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff35"><addr-line>IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff81"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom</addr-line></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="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation><nlm:aff id="aff82"><addr-line>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="aff82"><addr-line>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Aulchenko, Yurii S" sort="Aulchenko, Yurii S" uniqKey="Aulchenko Y" first="Yurii S." last="Aulchenko">Yurii S. Aulchenko</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff83"><addr-line>Croatian Centre for Global Health, Faculty of Medicine, University of Split, Split, Croatia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hastie, Nick" sort="Hastie, Nick" uniqKey="Hastie N" first="Nick" last="Hastie">Nick Hastie</name><affiliation><nlm:aff id="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Helmer, Catherine" sort="Helmer, Catherine" uniqKey="Helmer C" first="Catherine" last="Helmer">Catherine Helmer</name><affiliation><nlm:aff id="aff85"><addr-line>INSERM U897, Université Victor Ségalen Bordeaux 2, ISPED, Bordeaux, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff86"><addr-line>Université Bordeaux 2 Victor Segalen, Bordeaux, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="aff87"><addr-line>Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff88"><addr-line>Centre for Eye Research Australia (CERA), University of Melbourne, Melbourne, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ruggiero, Daniela" sort="Ruggiero, Daniela" uniqKey="Ruggiero D" first="Daniela" last="Ruggiero">Daniela Ruggiero</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bergmann, Sven" sort="Bergmann, Sven" uniqKey="Bergmann S" first="Sven" last="Bergmann">Sven Bergmann</name><affiliation><nlm:aff id="aff42"><addr-line>Swiss Institute of Bioinformatics, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="aff89"><addr-line>Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Viikari, Jorma" sort="Viikari, Jorma" uniqKey="Viikari J" first="Jorma" last="Viikari">Jorma Viikari</name><affiliation><nlm:aff id="aff90"><addr-line>Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nikopensius, Tiit" sort="Nikopensius, Tiit" uniqKey="Nikopensius T" first="Tiit" last="Nikopensius">Tiit Nikopensius</name><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Province, Michael" sort="Province, Michael" uniqKey="Province M" first="Michael" last="Province">Michael Province</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ketkar, Shamika" sort="Ketkar, Shamika" uniqKey="Ketkar S" first="Shamika" last="Ketkar">Shamika Ketkar</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Colhoun, Helen" sort="Colhoun, Helen" uniqKey="Colhoun H" first="Helen" last="Colhoun">Helen Colhoun</name><affiliation><nlm:aff id="aff46"><addr-line>Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Doney, Alex" sort="Doney, Alex" uniqKey="Doney A" first="Alex" last="Doney">Alex Doney</name><affiliation><nlm:aff id="aff91"><addr-line>NHS Tayside, Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Robino, Antonietta" sort="Robino, Antonietta" uniqKey="Robino A" first="Antonietta" last="Robino">Antonietta Robino</name><affiliation><nlm:aff id="aff92"><addr-line>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” University of Trieste, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Giulianini, Franco" sort="Giulianini, Franco" uniqKey="Giulianini F" first="Franco" last="Giulianini">Franco Giulianini</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kr Mer, Bernhard K" sort="Kr Mer, Bernhard K" uniqKey="Kr Mer B" first="Bernhard K." last="Kr Mer">Bernhard K. Kr Mer</name><affiliation><nlm:aff id="aff93"><addr-line>University Medical Centre Mannheim, 5th Department of Medicine, Mannheim, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Portas, Laura" sort="Portas, Laura" uniqKey="Portas L" first="Laura" last="Portas">Laura Portas</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="aff94"><addr-line>Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M." last="Buckley">Brendan M. Buckley</name><affiliation><nlm:aff id="aff95"><addr-line>Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Adam, Martin" sort="Adam, Martin" uniqKey="Adam M" first="Martin" last="Adam">Martin Adam</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Thun, Gian Andri" sort="Thun, Gian Andri" uniqKey="Thun G" first="Gian-Andri" last="Thun">Gian-Andri Thun</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Paulweber, Bernhard" sort="Paulweber, Bernhard" uniqKey="Paulweber B" first="Bernhard" last="Paulweber">Bernhard Paulweber</name><affiliation><nlm:aff id="aff96"><addr-line>First Department of Internal Medicine, Paracelsus Medical University, Salzburg, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Haun, Margot" sort="Haun, Margot" uniqKey="Haun M" first="Margot" last="Haun">Margot Haun</name><affiliation><nlm:aff id="aff97"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Metzger, Marie" sort="Metzger, Marie" uniqKey="Metzger M" first="Marie" last="Metzger">Marie Metzger</name><affiliation><nlm:aff id="aff98"><addr-line>Inserm UMRS 1018, CESP Team 10, Université Paris Sud, Villejuif, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="aff87"><addr-line>Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ciullo, Marina" sort="Ciullo, Marina" uniqKey="Ciullo M" first="Marina" last="Ciullo">Marina Ciullo</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kim, Stuart K" sort="Kim, Stuart K" uniqKey="Kim S" first="Stuart K." last="Kim">Stuart K. Kim</name><affiliation><nlm:aff id="aff29"><addr-line>Department of Developmental Biology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff68"><addr-line>Department of Genetics, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vollenweider, Peter" sort="Vollenweider, Peter" uniqKey="Vollenweider P" first="Peter" last="Vollenweider">Peter Vollenweider</name><affiliation><nlm:aff id="aff99"><addr-line>Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Raitakari, Olli" sort="Raitakari, Olli" uniqKey="Raitakari O" first="Olli" last="Raitakari">Olli Raitakari</name><affiliation><nlm:aff id="aff100"><addr-line>Research Centre of Applied and Preventive Cardiovascular Medicine, Department of Clinical Physiology, Turku University Hospital, University of Turku, Turku, Finland</addr-line></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="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin" sort="Palmer, Colin" uniqKey="Palmer C" first="Colin" last="Palmer">Colin Palmer</name><affiliation><nlm:aff id="aff101"><addr-line>Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom</addr-line></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="aff92"><addr-line>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” University of Trieste, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pirastu, Mario" sort="Pirastu, Mario" uniqKey="Pirastu M" first="Mario" last="Pirastu">Mario Pirastu</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J. Wouter" last="Jukema">J. Wouter Jukema</name><affiliation><nlm:aff id="aff50"><addr-line>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff102"><addr-line>Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff103"><addr-line>Einthoven Laboratory for Experimental Vascular Medicine, Leiden, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff104"><addr-line>Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Probst Hensch, Nicole M" sort="Probst Hensch, Nicole M" uniqKey="Probst Hensch N" first="Nicole M." last="Probst-Hensch">Nicole M. Probst-Hensch</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kronenberg, Florian" sort="Kronenberg, Florian" uniqKey="Kronenberg F" first="Florian" last="Kronenberg">Florian Kronenberg</name><affiliation><nlm:aff id="aff52"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shuldiner, Alan R" sort="Shuldiner, Alan R" uniqKey="Shuldiner A" first="Alan R." last="Shuldiner">Alan R. Shuldiner</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff105"><addr-line>Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coresh, Josef" sort="Coresh, Josef" uniqKey="Coresh J" first="Josef" last="Coresh">Josef Coresh</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff106"><addr-line>Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name><affiliation><nlm:aff id="aff57"><addr-line>Austrian Stroke Prevention Study, University Clinic of Neurology, Department of Special Neurology, Medical University Graz, Graz, Austria</addr-line></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="aff27"><addr-line>Clinical Research Branch, National Institute of Aging, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Siscovick, David S" sort="Siscovick, David S" uniqKey="Siscovick D" first="David S." last="Siscovick">David S. Siscovick</name><affiliation><nlm:aff id="aff28"><addr-line>University of Washington, Seattle, Washington, United States of America</addr-line></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="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Borecki, Ingrid" sort="Borecki, Ingrid" uniqKey="Borecki I" first="Ingrid" last="Borecki">Ingrid Borecki</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L. R." last="Kardia">Sharon L. R. Kardia</name><affiliation><nlm:aff id="aff107"><addr-line>Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="aff31"><addr-line>Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Curhan, Gary C" sort="Curhan, Gary C" uniqKey="Curhan G" first="Gary C." last="Curhan">Gary C. Curhan</name><affiliation><nlm:aff id="aff108"><addr-line>Brigham and Women's Hospital and Channing Laboratory, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gyllensten, Ulf" sort="Gyllensten, Ulf" uniqKey="Gyllensten U" first="Ulf" last="Gyllensten">Ulf Gyllensten</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Franke, Andre" sort="Franke, Andre" uniqKey="Franke A" first="Andre" last="Franke">Andre Franke</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rettig, Rainer" sort="Rettig, Rainer" uniqKey="Rettig R" first="Rainer" last="Rettig">Rainer Rettig</name><affiliation><nlm:aff id="aff109"><addr-line>Institute of Physiology, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Prokopenko, Inga" sort="Prokopenko, Inga" uniqKey="Prokopenko I" first="Inga" last="Prokopenko">Inga Prokopenko</name><affiliation><nlm:aff id="aff81"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul" sort="Ridker, Paul" uniqKey="Ridker P" first="Paul" last="Ridker">Paul Ridker</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff110"><addr-line>Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Parsa, Afshin" sort="Parsa, Afshin" uniqKey="Parsa A" first="Afshin" last="Parsa">Afshin Parsa</name><affiliation><nlm:aff id="aff111"><addr-line>Division of Nephrology, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bochud, Murielle" sort="Bochud, Murielle" uniqKey="Bochud M" first="Murielle" last="Bochud">Murielle Bochud</name><affiliation><nlm:aff id="aff112"><addr-line>University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Heid, Iris M" sort="Heid, Iris M" uniqKey="Heid I" first="Iris M." last="Heid">Iris M. Heid</name><affiliation><nlm:aff id="aff113"><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff114"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Goessling, Wolfram" sort="Goessling, Wolfram" uniqKey="Goessling W" first="Wolfram" last="Goessling">Wolfram Goessling</name><affiliation><nlm:aff id="aff115"><addr-line>Divisions of Genetics and Gastroenterology, Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff116"><addr-line>Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, United States of America</addr-line></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="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff110"><addr-line>Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kao, W H Linda" sort="Kao, W H Linda" uniqKey="Kao W" first="W. H. Linda" last="Kao">W. H. Linda Kao</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff106"><addr-line>Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fox, Caroline S" sort="Fox, Caroline S" uniqKey="Fox C" first="Caroline S." last="Fox">Caroline S. Fox</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff117"><addr-line>Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22479191</idno><idno type="pmc">3315455</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315455</idno><idno type="RBID">PMC:3315455</idno><idno type="doi">10.1371/journal.pgen.1002584</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002881</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002881</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function</title><author><name sortKey="Pattaro, Cristian" sort="Pattaro, Cristian" uniqKey="Pattaro C" first="Cristian" last="Pattaro">Cristian Pattaro</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kottgen, Anna" sort="Kottgen, Anna" uniqKey="Kottgen A" first="Anna" last="Köttgen">Anna Köttgen</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Teumer, Alexander" sort="Teumer, Alexander" uniqKey="Teumer A" first="Alexander" last="Teumer">Alexander Teumer</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Garnaas, Maija" sort="Garnaas, Maija" uniqKey="Garnaas M" first="Maija" last="Garnaas">Maija Garnaas</name><affiliation><nlm:aff id="aff5"><addr-line>Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Boger, Carsten A" sort="Boger, Carsten A" uniqKey="Boger C" first="Carsten A." last="Böger">Carsten A. Böger</name><affiliation><nlm:aff id="aff6"><addr-line>Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fuchsberger, Christian" sort="Fuchsberger, Christian" uniqKey="Fuchsberger C" first="Christian" last="Fuchsberger">Christian Fuchsberger</name><affiliation><nlm:aff id="aff7"><addr-line>Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Olden, Matthias" sort="Olden, Matthias" uniqKey="Olden M" first="Matthias" last="Olden">Matthias Olden</name><affiliation><nlm:aff id="aff8"><addr-line>Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><addr-line>Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chen, Ming Huei" sort="Chen, Ming Huei" uniqKey="Chen M" first="Ming-Huei" last="Chen">Ming-Huei Chen</name><affiliation><nlm:aff id="aff10"><addr-line>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tin, Adrienne" sort="Tin, Adrienne" uniqKey="Tin A" first="Adrienne" last="Tin">Adrienne Tin</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Taliun, Daniel" sort="Taliun, Daniel" uniqKey="Taliun D" first="Daniel" last="Taliun">Daniel Taliun</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gao, Xiaoyi" sort="Gao, Xiaoyi" uniqKey="Gao X" first="Xiaoyi" last="Gao">Xiaoyi Gao</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gorski, Mathias" sort="Gorski, Mathias" uniqKey="Gorski M" first="Mathias" last="Gorski">Mathias Gorski</name><affiliation><nlm:aff id="aff13"><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="aff15"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hundertmark, Claudia" sort="Hundertmark, Claudia" uniqKey="Hundertmark C" first="Claudia" last="Hundertmark">Claudia Hundertmark</name><affiliation><nlm:aff id="aff16"><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Foster, Meredith C" sort="Foster, Meredith C" uniqKey="Foster M" first="Meredith C." last="Foster">Meredith C. Foster</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="O Seaghdha, Conall M" sort="O Seaghdha, Conall M" uniqKey="O Seaghdha C" first="Conall M." last="O'Seaghdha">Conall M. O'Seaghdha</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff18"><addr-line>Division of Nephrology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></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="aff19"><addr-line>Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Isaacs, Aaron" sort="Isaacs, Aaron" uniqKey="Isaacs A" first="Aaron" last="Isaacs">Aaron Isaacs</name><affiliation><nlm:aff id="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff21"><addr-line>Centre for Medical Systems Biology, Leiden, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="aff22"><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="O Connell, Jeffrey R" sort="O Connell, Jeffrey R" uniqKey="O Connell J" first="Jeffrey R." last="O'Connell">Jeffrey R. O'Connell</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Struchalin, Maksim" sort="Struchalin, Maksim" uniqKey="Struchalin M" first="Maksim" last="Struchalin">Maksim Struchalin</name><affiliation><nlm:aff id="aff26"><addr-line>Department of Epidemiology and Biostatistics and Department of Forensic Molecular Biology, Erasmus University Medical Centre, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tanaka, Toshiko" sort="Tanaka, Toshiko" uniqKey="Tanaka T" first="Toshiko" last="Tanaka">Toshiko Tanaka</name><affiliation><nlm:aff id="aff27"><addr-line>Clinical Research Branch, National Institute of Aging, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Guo" sort="Li, Guo" uniqKey="Li G" first="Guo" last="Li">Guo Li</name><affiliation><nlm:aff id="aff28"><addr-line>University of Washington, Seattle, Washington, United States of America</addr-line></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="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gierman, Hinco J" sort="Gierman, Hinco J" uniqKey="Gierman H" first="Hinco J." last="Gierman">Hinco J. Gierman</name><affiliation><nlm:aff id="aff29"><addr-line>Department of Developmental Biology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Feitosa, Mary" sort="Feitosa, Mary" uniqKey="Feitosa M" first="Mary" last="Feitosa">Mary Feitosa</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Atkinson, Elizabeth J" sort="Atkinson, Elizabeth J" uniqKey="Atkinson E" first="Elizabeth J." last="Atkinson">Elizabeth J. Atkinson</name><affiliation><nlm:aff id="aff30"><addr-line>Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="aff31"><addr-line>Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></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="aff32"><addr-line>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Johansson, Sa" sort="Johansson, Sa" uniqKey="Johansson " first=" Sa" last="Johansson"> Sa Johansson</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tonjes, Anke" sort="Tonjes, Anke" uniqKey="Tonjes A" first="Anke" last="Tönjes">Anke Tönjes</name><affiliation><nlm:aff id="aff34"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff35"><addr-line>IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chouraki, Vincent" sort="Chouraki, Vincent" uniqKey="Chouraki V" first="Vincent" last="Chouraki">Vincent Chouraki</name><affiliation><nlm:aff id="aff37"><addr-line>Inserm UMR744, Institut Pasteur, Lille, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Holliday, Elizabeth G" sort="Holliday, Elizabeth G" uniqKey="Holliday E" first="Elizabeth G." last="Holliday">Elizabeth G. Holliday</name><affiliation><nlm:aff id="aff38"><addr-line>Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, Australia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff39"><addr-line>Centre for Information-based Medicine, Hunter Medical Research Institute, Newcastle, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Sorice, Rossella" sort="Sorice, Rossella" uniqKey="Sorice R" first="Rossella" last="Sorice">Rossella Sorice</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltan" last="Kutalik">Zoltan Kutalik</name><affiliation><nlm:aff id="aff41"><addr-line>Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff42"><addr-line>Swiss Institute of Bioinformatics, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="aff43"><addr-line>Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Centre for Laboratory Medicine Tampere Finn-Medi 2, Tampere, Finland</addr-line></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="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Deshmukh, Harshal" sort="Deshmukh, Harshal" uniqKey="Deshmukh H" first="Harshal" last="Deshmukh">Harshal Deshmukh</name><affiliation><nlm:aff id="aff46"><addr-line>Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></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="aff47"><addr-line>Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Chu, Audrey Y" sort="Chu, Audrey Y" uniqKey="Chu A" first="Audrey Y." last="Chu">Audrey Y. Chu</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Murgia, Federico" sort="Murgia, Federico" uniqKey="Murgia F" first="Federico" last="Murgia">Federico Murgia</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="aff50"><addr-line>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Imboden, Medea" sort="Imboden, Medea" uniqKey="Imboden M" first="Medea" last="Imboden">Medea Imboden</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kollerits, Barbara" sort="Kollerits, Barbara" uniqKey="Kollerits B" first="Barbara" last="Kollerits">Barbara Kollerits</name><affiliation><nlm:aff id="aff52"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></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="aff54"><addr-line>Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland, United States of America</addr-line></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="aff54"><addr-line>Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland, United States of America</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></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="aff55"><addr-line>Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name><affiliation><nlm:aff id="aff56"><addr-line>Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry and Department of Neurology, Medical University Graz, Graz, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Cavalieri, Margherita" sort="Cavalieri, Margherita" uniqKey="Cavalieri M" first="Margherita" last="Cavalieri">Margherita Cavalieri</name><affiliation><nlm:aff id="aff57"><addr-line>Austrian Stroke Prevention Study, University Clinic of Neurology, Department of Special Neurology, Medical University Graz, Graz, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rao, Madhumathi" sort="Rao, Madhumathi" uniqKey="Rao M" first="Madhumathi" last="Rao">Madhumathi Rao</name><affiliation><nlm:aff id="aff58"><addr-line>Division of Nephrology/Tufts Evidence Practice Center, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America</addr-line></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="aff32"><addr-line>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Demirkan, Ayse" sort="Demirkan, Ayse" uniqKey="Demirkan A" first="Ayse" last="Demirkan">Ayse Demirkan</name><affiliation><nlm:aff id="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="De Andrade, Mariza" sort="De Andrade, Mariza" uniqKey="De Andrade M" first="Mariza" last="De Andrade">Mariza De Andrade</name><affiliation><nlm:aff id="aff30"><addr-line>Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Turner, Stephen T" sort="Turner, Stephen T" uniqKey="Turner S" first="Stephen T." last="Turner">Stephen T. Turner</name><affiliation><nlm:aff id="aff59"><addr-line>Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ding, Jingzhong" sort="Ding, Jingzhong" uniqKey="Ding J" first="Jingzhong" last="Ding">Jingzhong Ding</name><affiliation><nlm:aff id="aff60"><addr-line>Department of Internal Medicine/Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Andrews, Jeanette S" sort="Andrews, Jeanette S" uniqKey="Andrews J" first="Jeanette S." last="Andrews">Jeanette S. Andrews</name><affiliation><nlm:aff id="aff61"><addr-line>Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Freedman, Barry I" sort="Freedman, Barry I" uniqKey="Freedman B" first="Barry I." last="Freedman">Barry I. Freedman</name><affiliation><nlm:aff id="aff62"><addr-line>Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Koenig, Wolfgang" sort="Koenig, Wolfgang" uniqKey="Koenig W" first="Wolfgang" last="Koenig">Wolfgang Koenig</name><affiliation><nlm:aff id="aff63"><addr-line>Abteilung Innere II, Universitätsklinikum Ulm, Ulm, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation><nlm:aff id="aff64"><addr-line>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Doring, Angela" sort="Doring, Angela" uniqKey="Doring A" first="Angela" last="Döring">Angela Döring</name><affiliation><nlm:aff id="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff64"><addr-line>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></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="aff14"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff65"><addr-line>Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff66"><addr-line>Klinikum Grosshadern, Neuherberg, Germany</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></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="aff67"><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Minelli, Cosetta" sort="Minelli, Cosetta" uniqKey="Minelli C" first="Cosetta" last="Minelli">Cosetta Minelli</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wheeler, Heather E" sort="Wheeler, Heather E" uniqKey="Wheeler H" first="Heather E." last="Wheeler">Heather E. Wheeler</name><affiliation><nlm:aff id="aff68"><addr-line>Department of Genetics, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff69"><addr-line>Department of Medicine, University of Chicago, Chicago, Illinois, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Igl, Wilmar" sort="Igl, Wilmar" uniqKey="Igl W" first="Wilmar" last="Igl">Wilmar Igl</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Zaboli, Ghazal" sort="Zaboli, Ghazal" uniqKey="Zaboli G" first="Ghazal" last="Zaboli">Ghazal Zaboli</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wild, Sarah H" sort="Wild, Sarah H" uniqKey="Wild S" first="Sarah H." last="Wild">Sarah H. Wild</name><affiliation><nlm:aff id="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></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="aff71"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ellinghaus, David" sort="Ellinghaus, David" uniqKey="Ellinghaus D" first="David" last="Ellinghaus">David Ellinghaus</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nothlings, Ute" sort="Nothlings, Ute" uniqKey="Nothlings U" first="Ute" last="Nöthlings">Ute Nöthlings</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff73"><addr-line>popgen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jacobs, Gunnar" sort="Jacobs, Gunnar" uniqKey="Jacobs G" first="Gunnar" last="Jacobs">Gunnar Jacobs</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff73"><addr-line>popgen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Biffar, Reiner" sort="Biffar, Reiner" uniqKey="Biffar R" first="Reiner" last="Biffar">Reiner Biffar</name><affiliation><nlm:aff id="aff74"><addr-line>Clinic for Prosthodontic Dentistry, Gerostomatology, and Material Science, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Endlich, Karlhans" sort="Endlich, Karlhans" uniqKey="Endlich K" first="Karlhans" last="Endlich">Karlhans Endlich</name><affiliation><nlm:aff id="aff75"><addr-line>Institute of Anatomy and Cell Biology, University of Greifswald, Greifswald, Germany</addr-line></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="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kroemer, Heyo K" sort="Kroemer, Heyo K" uniqKey="Kroemer H" first="Heyo K." last="Kroemer">Heyo K. Kroemer</name><affiliation><nlm:aff id="aff76"><addr-line>Institute of Pharmacology, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nauck, Matthias" sort="Nauck, Matthias" uniqKey="Nauck M" first="Matthias" last="Nauck">Matthias Nauck</name><affiliation><nlm:aff id="aff77"><addr-line>Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stracke, Sylvia" sort="Stracke, Sylvia" uniqKey="Stracke S" first="Sylvia" last="Stracke">Sylvia Stracke</name><affiliation><nlm:aff id="aff78"><addr-line>Clinic for Internal Medicine A, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Volker, Uwe" sort="Volker, Uwe" uniqKey="Volker U" first="Uwe" last="Völker">Uwe Völker</name><affiliation><nlm:aff id="aff4"><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></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="aff79"><addr-line>Institute for Community Medicine, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kovacs, Peter" sort="Kovacs, Peter" uniqKey="Kovacs P" first="Peter" last="Kovacs">Peter Kovacs</name><affiliation><nlm:aff id="aff80"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Stumvoll, Michael" sort="Stumvoll, Michael" uniqKey="Stumvoll M" first="Michael" last="Stumvoll">Michael Stumvoll</name><affiliation><nlm:aff id="aff34"><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff35"><addr-line>IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="M Gi, Reedik" sort="M Gi, Reedik" uniqKey="M Gi R" first="Reedik" last="M Gi">Reedik M Gi</name><affiliation><nlm:aff id="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff81"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom</addr-line></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="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation><nlm:aff id="aff82"><addr-line>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="aff82"><addr-line>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Aulchenko, Yurii S" sort="Aulchenko, Yurii S" uniqKey="Aulchenko Y" first="Yurii S." last="Aulchenko">Yurii S. Aulchenko</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff83"><addr-line>Croatian Centre for Global Health, Faculty of Medicine, University of Split, Split, Croatia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Hastie, Nick" sort="Hastie, Nick" uniqKey="Hastie N" first="Nick" last="Hastie">Nick Hastie</name><affiliation><nlm:aff id="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name><affiliation><nlm:aff id="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Helmer, Catherine" sort="Helmer, Catherine" uniqKey="Helmer C" first="Catherine" last="Helmer">Catherine Helmer</name><affiliation><nlm:aff id="aff85"><addr-line>INSERM U897, Université Victor Ségalen Bordeaux 2, ISPED, Bordeaux, France</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff86"><addr-line>Université Bordeaux 2 Victor Segalen, Bordeaux, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wang, Jie Jin" sort="Wang, Jie Jin" uniqKey="Wang J" first="Jie Jin" last="Wang">Jie Jin Wang</name><affiliation><nlm:aff id="aff87"><addr-line>Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff88"><addr-line>Centre for Eye Research Australia (CERA), University of Melbourne, Melbourne, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ruggiero, Daniela" sort="Ruggiero, Daniela" uniqKey="Ruggiero D" first="Daniela" last="Ruggiero">Daniela Ruggiero</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bergmann, Sven" sort="Bergmann, Sven" uniqKey="Bergmann S" first="Sven" last="Bergmann">Sven Bergmann</name><affiliation><nlm:aff id="aff42"><addr-line>Swiss Institute of Bioinformatics, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="aff89"><addr-line>Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Viikari, Jorma" sort="Viikari, Jorma" uniqKey="Viikari J" first="Jorma" last="Viikari">Jorma Viikari</name><affiliation><nlm:aff id="aff90"><addr-line>Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Nikopensius, Tiit" sort="Nikopensius, Tiit" uniqKey="Nikopensius T" first="Tiit" last="Nikopensius">Tiit Nikopensius</name><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Province, Michael" sort="Province, Michael" uniqKey="Province M" first="Michael" last="Province">Michael Province</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ketkar, Shamika" sort="Ketkar, Shamika" uniqKey="Ketkar S" first="Shamika" last="Ketkar">Shamika Ketkar</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Colhoun, Helen" sort="Colhoun, Helen" uniqKey="Colhoun H" first="Helen" last="Colhoun">Helen Colhoun</name><affiliation><nlm:aff id="aff46"><addr-line>Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Doney, Alex" sort="Doney, Alex" uniqKey="Doney A" first="Alex" last="Doney">Alex Doney</name><affiliation><nlm:aff id="aff91"><addr-line>NHS Tayside, Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Robino, Antonietta" sort="Robino, Antonietta" uniqKey="Robino A" first="Antonietta" last="Robino">Antonietta Robino</name><affiliation><nlm:aff id="aff92"><addr-line>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” University of Trieste, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Giulianini, Franco" sort="Giulianini, Franco" uniqKey="Giulianini F" first="Franco" last="Giulianini">Franco Giulianini</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kr Mer, Bernhard K" sort="Kr Mer, Bernhard K" uniqKey="Kr Mer B" first="Bernhard K." last="Kr Mer">Bernhard K. Kr Mer</name><affiliation><nlm:aff id="aff93"><addr-line>University Medical Centre Mannheim, 5th Department of Medicine, Mannheim, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Portas, Laura" sort="Portas, Laura" uniqKey="Portas L" first="Laura" last="Portas">Laura Portas</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="aff94"><addr-line>Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M." last="Buckley">Brendan M. Buckley</name><affiliation><nlm:aff id="aff95"><addr-line>Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Adam, Martin" sort="Adam, Martin" uniqKey="Adam M" first="Martin" last="Adam">Martin Adam</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Thun, Gian Andri" sort="Thun, Gian Andri" uniqKey="Thun G" first="Gian-Andri" last="Thun">Gian-Andri Thun</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Paulweber, Bernhard" sort="Paulweber, Bernhard" uniqKey="Paulweber B" first="Bernhard" last="Paulweber">Bernhard Paulweber</name><affiliation><nlm:aff id="aff96"><addr-line>First Department of Internal Medicine, Paracelsus Medical University, Salzburg, Austria</addr-line></nlm:aff></affiliation></author><author><name sortKey="Haun, Margot" sort="Haun, Margot" uniqKey="Haun M" first="Margot" last="Haun">Margot Haun</name><affiliation><nlm:aff id="aff97"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Metzger, Marie" sort="Metzger, Marie" uniqKey="Metzger M" first="Marie" last="Metzger">Marie Metzger</name><affiliation><nlm:aff id="aff98"><addr-line>Inserm UMRS 1018, CESP Team 10, Université Paris Sud, Villejuif, France</addr-line></nlm:aff></affiliation></author><author><name sortKey="Mitchell, Paul" sort="Mitchell, Paul" uniqKey="Mitchell P" first="Paul" last="Mitchell">Paul Mitchell</name><affiliation><nlm:aff id="aff87"><addr-line>Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ciullo, Marina" sort="Ciullo, Marina" uniqKey="Ciullo M" first="Marina" last="Ciullo">Marina Ciullo</name><affiliation><nlm:aff id="aff40"><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kim, Stuart K" sort="Kim, Stuart K" uniqKey="Kim S" first="Stuart K." last="Kim">Stuart K. Kim</name><affiliation><nlm:aff id="aff29"><addr-line>Department of Developmental Biology, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff68"><addr-line>Department of Genetics, Stanford University, Stanford, California, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vollenweider, Peter" sort="Vollenweider, Peter" uniqKey="Vollenweider P" first="Peter" last="Vollenweider">Peter Vollenweider</name><affiliation><nlm:aff id="aff99"><addr-line>Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Raitakari, Olli" sort="Raitakari, Olli" uniqKey="Raitakari O" first="Olli" last="Raitakari">Olli Raitakari</name><affiliation><nlm:aff id="aff100"><addr-line>Research Centre of Applied and Preventive Cardiovascular Medicine, Department of Clinical Physiology, Turku University Hospital, University of Turku, Turku, Finland</addr-line></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="aff44"><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff45"><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></nlm:aff></affiliation></author><author><name sortKey="Palmer, Colin" sort="Palmer, Colin" uniqKey="Palmer C" first="Colin" last="Palmer">Colin Palmer</name><affiliation><nlm:aff id="aff101"><addr-line>Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom</addr-line></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="aff92"><addr-line>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” University of Trieste, Trieste, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pirastu, Mario" sort="Pirastu, Mario" uniqKey="Pirastu M" first="Mario" last="Pirastu">Mario Pirastu</name><affiliation><nlm:aff id="aff49"><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J. Wouter" last="Jukema">J. Wouter Jukema</name><affiliation><nlm:aff id="aff50"><addr-line>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff102"><addr-line>Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff103"><addr-line>Einthoven Laboratory for Experimental Vascular Medicine, Leiden, The Netherlands</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff104"><addr-line>Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Probst Hensch, Nicole M" sort="Probst Hensch, Nicole M" uniqKey="Probst Hensch N" first="Nicole M." last="Probst-Hensch">Nicole M. Probst-Hensch</name><affiliation><nlm:aff id="aff51"><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kronenberg, Florian" sort="Kronenberg, Florian" uniqKey="Kronenberg F" first="Florian" last="Kronenberg">Florian Kronenberg</name><affiliation><nlm:aff id="aff52"><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></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="aff53"><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></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="aff23"><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shuldiner, Alan R" sort="Shuldiner, Alan R" uniqKey="Shuldiner A" first="Alan R." last="Shuldiner">Alan R. Shuldiner</name><affiliation><nlm:aff id="aff25"><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff105"><addr-line>Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coresh, Josef" sort="Coresh, Josef" uniqKey="Coresh J" first="Josef" last="Coresh">Josef Coresh</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff106"><addr-line>Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name><affiliation><nlm:aff id="aff57"><addr-line>Austrian Stroke Prevention Study, University Clinic of Neurology, Department of Special Neurology, Medical University Graz, Graz, Austria</addr-line></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="aff27"><addr-line>Clinical Research Branch, National Institute of Aging, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Siscovick, David S" sort="Siscovick, David S" uniqKey="Siscovick D" first="David S." last="Siscovick">David S. Siscovick</name><affiliation><nlm:aff id="aff28"><addr-line>University of Washington, Seattle, Washington, United States of America</addr-line></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="aff20"><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff></affiliation></author><author><name sortKey="Borecki, Ingrid" sort="Borecki, Ingrid" uniqKey="Borecki I" first="Ingrid" last="Borecki">Ingrid Borecki</name><affiliation><nlm:aff id="aff12"><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L. R." last="Kardia">Sharon L. R. Kardia</name><affiliation><nlm:aff id="aff107"><addr-line>Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="aff31"><addr-line>Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Curhan, Gary C" sort="Curhan, Gary C" uniqKey="Curhan G" first="Gary C." last="Curhan">Gary C. Curhan</name><affiliation><nlm:aff id="aff108"><addr-line>Brigham and Women's Hospital and Channing Laboratory, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gyllensten, Ulf" sort="Gyllensten, Ulf" uniqKey="Gyllensten U" first="Ulf" last="Gyllensten">Ulf Gyllensten</name><affiliation><nlm:aff id="aff33"><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></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="aff70"><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Franke, Andre" sort="Franke, Andre" uniqKey="Franke A" first="Andre" last="Franke">Andre Franke</name><affiliation><nlm:aff id="aff72"><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name><affiliation><nlm:aff id="aff1"><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></nlm:aff></affiliation></author><author><name sortKey="Rettig, Rainer" sort="Rettig, Rainer" uniqKey="Rettig R" first="Rainer" last="Rettig">Rainer Rettig</name><affiliation><nlm:aff id="aff109"><addr-line>Institute of Physiology, University of Greifswald, Greifswald, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Prokopenko, Inga" sort="Prokopenko, Inga" uniqKey="Prokopenko I" first="Inga" last="Prokopenko">Inga Prokopenko</name><affiliation><nlm:aff id="aff81"><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name><affiliation><nlm:aff id="aff36"><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></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="aff84"><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul" sort="Ridker, Paul" uniqKey="Ridker P" first="Paul" last="Ridker">Paul Ridker</name><affiliation><nlm:aff id="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff110"><addr-line>Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Parsa, Afshin" sort="Parsa, Afshin" uniqKey="Parsa A" first="Afshin" last="Parsa">Afshin Parsa</name><affiliation><nlm:aff id="aff111"><addr-line>Division of Nephrology, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Bochud, Murielle" sort="Bochud, Murielle" uniqKey="Bochud M" first="Murielle" last="Bochud">Murielle Bochud</name><affiliation><nlm:aff id="aff112"><addr-line>University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland</addr-line></nlm:aff></affiliation></author><author><name sortKey="Heid, Iris M" sort="Heid, Iris M" uniqKey="Heid I" first="Iris M." last="Heid">Iris M. Heid</name><affiliation><nlm:aff id="aff113"><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff114"><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff></affiliation></author><author><name sortKey="Goessling, Wolfram" sort="Goessling, Wolfram" uniqKey="Goessling W" first="Wolfram" last="Goessling">Wolfram Goessling</name><affiliation><nlm:aff id="aff115"><addr-line>Divisions of Genetics and Gastroenterology, Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff116"><addr-line>Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, United States of America</addr-line></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="aff48"><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff110"><addr-line>Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Kao, W H Linda" sort="Kao, W H Linda" uniqKey="Kao W" first="W. H. Linda" last="Kao">W. H. Linda Kao</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff106"><addr-line>Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fox, Caroline S" sort="Fox, Caroline S" uniqKey="Fox C" first="Caroline S." last="Fox">Caroline S. Fox</name><affiliation><nlm:aff id="aff17"><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="aff117"><addr-line>Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS Genetics</title><idno type="ISSN">1553-7390</idno><idno type="eISSN">1553-7404</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>Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near <italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>SLC47A1</italic>, <italic>CDK12</italic>, <italic>CASP9</italic>, and <italic>INO80</italic>. Morpholino knockdown of <italic>mpped2</italic> and <italic>casp9</italic> in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Genet</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Genet</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosgen</journal-id><journal-title-group><journal-title>PLoS Genetics</journal-title></journal-title-group><issn pub-type="ppub">1553-7390</issn><issn pub-type="epub">1553-7404</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22479191</article-id><article-id pub-id-type="pmc">3315455</article-id><article-id pub-id-type="publisher-id">PGENETICS-D-11-02100</article-id><article-id pub-id-type="doi">10.1371/journal.pgen.1002584</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Genetics</subject></subj-group></subj-group></article-categories><title-group><article-title>Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function</article-title><alt-title alt-title-type="running-head">GWAS Reveals New Loci for Kidney Function</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Pattaro</surname><given-names>Cristian</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Köttgen</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Teumer</surname><given-names>Alexander</given-names></name><xref ref-type="aff" 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rid="aff11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tin</surname><given-names>Adrienne</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Taliun</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Man</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Xiaoyi</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gorski</surname><given-names>Mathias</given-names></name><xref ref-type="aff" rid="aff13"><sup>13</sup></xref><xref ref-type="aff" rid="aff14"><sup>14</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Qiong</given-names></name><xref ref-type="aff" rid="aff15"><sup>15</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hundertmark</surname><given-names>Claudia</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Foster</surname><given-names>Meredith C.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>O'Seaghdha</surname><given-names>Conall M.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref><xref ref-type="aff" rid="aff18"><sup>18</sup></xref></contrib><contrib contrib-type="author"><name><surname>Glazer</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="aff19"><sup>19</sup></xref></contrib><contrib contrib-type="author"><name><surname>Isaacs</surname><given-names>Aaron</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref><xref ref-type="aff" rid="aff21"><sup>21</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Ching-Ti</given-names></name><xref ref-type="aff" rid="aff22"><sup>22</sup></xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Albert V.</given-names></name><xref ref-type="aff" rid="aff23"><sup>23</sup></xref><xref ref-type="aff" rid="aff24"><sup>24</sup></xref></contrib><contrib contrib-type="author"><name><surname>O'Connell</surname><given-names>Jeffrey R.</given-names></name><xref ref-type="aff" rid="aff25"><sup>25</sup></xref></contrib><contrib contrib-type="author"><name><surname>Struchalin</surname><given-names>Maksim</given-names></name><xref ref-type="aff" rid="aff26"><sup>26</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tanaka</surname><given-names>Toshiko</given-names></name><xref ref-type="aff" rid="aff27"><sup>27</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Guo</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Andrew D.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gierman</surname><given-names>Hinco J.</given-names></name><xref ref-type="aff" rid="aff29"><sup>29</sup></xref></contrib><contrib contrib-type="author"><name><surname>Feitosa</surname><given-names>Mary</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hwang</surname><given-names>Shih-Jen</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Atkinson</surname><given-names>Elizabeth J.</given-names></name><xref ref-type="aff" 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contrib-type="author"><name><surname>Schmidt</surname><given-names>Helena</given-names></name><xref ref-type="aff" rid="aff56"><sup>56</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cavalieri</surname><given-names>Margherita</given-names></name><xref ref-type="aff" rid="aff57"><sup>57</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rao</surname><given-names>Madhumathi</given-names></name><xref ref-type="aff" rid="aff58"><sup>58</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>Frank B.</given-names></name><xref ref-type="aff" rid="aff32"><sup>32</sup></xref></contrib><contrib contrib-type="author"><name><surname>Demirkan</surname><given-names>Ayse</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>Oostra</surname><given-names>Ben A.</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>de Andrade</surname><given-names>Mariza</given-names></name><xref ref-type="aff" rid="aff30"><sup>30</sup></xref></contrib><contrib contrib-type="author"><name><surname>Turner</surname><given-names>Stephen T.</given-names></name><xref ref-type="aff" rid="aff59"><sup>59</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ding</surname><given-names>Jingzhong</given-names></name><xref ref-type="aff" rid="aff60"><sup>60</sup></xref></contrib><contrib contrib-type="author"><name><surname>Andrews</surname><given-names>Jeanette S.</given-names></name><xref ref-type="aff" rid="aff61"><sup>61</sup></xref></contrib><contrib contrib-type="author"><name><surname>Freedman</surname><given-names>Barry I.</given-names></name><xref ref-type="aff" rid="aff62"><sup>62</sup></xref></contrib><contrib contrib-type="author"><name><surname>Koenig</surname><given-names>Wolfgang</given-names></name><xref ref-type="aff" rid="aff63"><sup>63</sup></xref></contrib><contrib contrib-type="author"><name><surname>Illig</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff64"><sup>64</sup></xref></contrib><contrib contrib-type="author"><name><surname>Döring</surname><given-names>Angela</given-names></name><xref ref-type="aff" rid="aff14"><sup>14</sup></xref><xref ref-type="aff" rid="aff64"><sup>64</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wichmann</surname><given-names>H.-Erich</given-names></name><xref ref-type="aff" rid="aff14"><sup>14</sup></xref><xref ref-type="aff" rid="aff65"><sup>65</sup></xref><xref ref-type="aff" rid="aff66"><sup>66</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kolcic</surname><given-names>Ivana</given-names></name><xref ref-type="aff" rid="aff67"><sup>67</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zemunik</surname><given-names>Tatijana</given-names></name><xref ref-type="aff" rid="aff67"><sup>67</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boban</surname><given-names>Mladen</given-names></name><xref ref-type="aff" rid="aff67"><sup>67</sup></xref></contrib><contrib contrib-type="author"><name><surname>Minelli</surname><given-names>Cosetta</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wheeler</surname><given-names>Heather E.</given-names></name><xref ref-type="aff" rid="aff68"><sup>68</sup></xref><xref ref-type="aff" rid="aff69"><sup>69</sup></xref></contrib><contrib contrib-type="author"><name><surname>Igl</surname><given-names>Wilmar</given-names></name><xref ref-type="aff" rid="aff33"><sup>33</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zaboli</surname><given-names>Ghazal</given-names></name><xref ref-type="aff" rid="aff33"><sup>33</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wild</surname><given-names>Sarah H.</given-names></name><xref ref-type="aff" rid="aff70"><sup>70</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wright</surname><given-names>Alan F.</given-names></name><xref ref-type="aff" rid="aff71"><sup>71</sup></xref></contrib><contrib contrib-type="author"><name><surname>Campbell</surname><given-names>Harry</given-names></name><xref ref-type="aff" rid="aff70"><sup>70</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ellinghaus</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff72"><sup>72</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nöthlings</surname><given-names>Ute</given-names></name><xref ref-type="aff" rid="aff72"><sup>72</sup></xref><xref ref-type="aff" rid="aff73"><sup>73</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jacobs</surname><given-names>Gunnar</given-names></name><xref ref-type="aff" rid="aff72"><sup>72</sup></xref><xref ref-type="aff" rid="aff73"><sup>73</sup></xref></contrib><contrib contrib-type="author"><name><surname>Biffar</surname><given-names>Reiner</given-names></name><xref ref-type="aff" rid="aff74"><sup>74</sup></xref></contrib><contrib contrib-type="author"><name><surname>Endlich</surname><given-names>Karlhans</given-names></name><xref ref-type="aff" rid="aff75"><sup>75</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ernst</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Homuth</surname><given-names>Georg</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kroemer</surname><given-names>Heyo K.</given-names></name><xref ref-type="aff" rid="aff76"><sup>76</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nauck</surname><given-names>Matthias</given-names></name><xref ref-type="aff" rid="aff77"><sup>77</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stracke</surname><given-names>Sylvia</given-names></name><xref ref-type="aff" rid="aff78"><sup>78</sup></xref></contrib><contrib contrib-type="author"><name><surname>Völker</surname><given-names>Uwe</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Völzke</surname><given-names>Henry</given-names></name><xref ref-type="aff" rid="aff79"><sup>79</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kovacs</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff80"><sup>80</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stumvoll</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff34"><sup>34</sup></xref><xref ref-type="aff" rid="aff35"><sup>35</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mägi</surname><given-names>Reedik</given-names></name><xref ref-type="aff" rid="aff44"><sup>44</sup></xref><xref ref-type="aff" rid="aff81"><sup>81</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hofman</surname><given-names>Albert</given-names></name><xref ref-type="aff" rid="aff36"><sup>36</sup></xref></contrib><contrib contrib-type="author"><name><surname>Uitterlinden</surname><given-names>Andre G.</given-names></name><xref ref-type="aff" rid="aff82"><sup>82</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rivadeneira</surname><given-names>Fernando</given-names></name><xref ref-type="aff" rid="aff82"><sup>82</sup></xref></contrib><contrib contrib-type="author"><name><surname>Aulchenko</surname><given-names>Yurii S.</given-names></name><xref ref-type="aff" rid="aff36"><sup>36</sup></xref></contrib><contrib contrib-type="author"><name><surname>Polasek</surname><given-names>Ozren</given-names></name><xref ref-type="aff" rid="aff83"><sup>83</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hastie</surname><given-names>Nick</given-names></name><xref ref-type="aff" rid="aff84"><sup>84</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vitart</surname><given-names>Veronique</given-names></name><xref ref-type="aff" rid="aff84"><sup>84</sup></xref></contrib><contrib contrib-type="author"><name><surname>Helmer</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="aff85"><sup>85</sup></xref><xref ref-type="aff" rid="aff86"><sup>86</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jie Jin</given-names></name><xref ref-type="aff" rid="aff87"><sup>87</sup></xref><xref ref-type="aff" rid="aff88"><sup>88</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ruggiero</surname><given-names>Daniela</given-names></name><xref ref-type="aff" rid="aff40"><sup>40</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bergmann</surname><given-names>Sven</given-names></name><xref ref-type="aff" rid="aff42"><sup>42</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kähönen</surname><given-names>Mika</given-names></name><xref ref-type="aff" rid="aff89"><sup>89</sup></xref></contrib><contrib contrib-type="author"><name><surname>Viikari</surname><given-names>Jorma</given-names></name><xref ref-type="aff" rid="aff90"><sup>90</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nikopensius</surname><given-names>Tiit</given-names></name><xref ref-type="aff" rid="aff45"><sup>45</sup></xref></contrib><contrib contrib-type="author"><name><surname>Province</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ketkar</surname><given-names>Shamika</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Colhoun</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="aff46"><sup>46</sup></xref></contrib><contrib contrib-type="author"><name><surname>Doney</surname><given-names>Alex</given-names></name><xref ref-type="aff" rid="aff91"><sup>91</sup></xref></contrib><contrib contrib-type="author"><name><surname>Robino</surname><given-names>Antonietta</given-names></name><xref ref-type="aff" rid="aff92"><sup>92</sup></xref></contrib><contrib contrib-type="author"><name><surname>Giulianini</surname><given-names>Franco</given-names></name><xref ref-type="aff" rid="aff48"><sup>48</sup></xref></contrib><contrib contrib-type="author"><name><surname>Krämer</surname><given-names>Bernhard K.</given-names></name><xref ref-type="aff" rid="aff93"><sup>93</sup></xref></contrib><contrib contrib-type="author"><name><surname>Portas</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff49"><sup>49</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ford</surname><given-names>Ian</given-names></name><xref ref-type="aff" rid="aff94"><sup>94</sup></xref></contrib><contrib contrib-type="author"><name><surname>Buckley</surname><given-names>Brendan M.</given-names></name><xref ref-type="aff" rid="aff95"><sup>95</sup></xref></contrib><contrib contrib-type="author"><name><surname>Adam</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="aff51"><sup>51</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thun</surname><given-names>Gian-Andri</given-names></name><xref ref-type="aff" rid="aff51"><sup>51</sup></xref></contrib><contrib contrib-type="author"><name><surname>Paulweber</surname><given-names>Bernhard</given-names></name><xref ref-type="aff" rid="aff96"><sup>96</sup></xref></contrib><contrib contrib-type="author"><name><surname>Haun</surname><given-names>Margot</given-names></name><xref ref-type="aff" rid="aff97"><sup>97</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sala</surname><given-names>Cinzia</given-names></name><xref ref-type="aff" rid="aff53"><sup>53</sup></xref></contrib><contrib contrib-type="author"><name><surname>Metzger</surname><given-names>Marie</given-names></name><xref ref-type="aff" rid="aff98"><sup>98</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mitchell</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff87"><sup>87</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ciullo</surname><given-names>Marina</given-names></name><xref ref-type="aff" rid="aff40"><sup>40</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Stuart K.</given-names></name><xref ref-type="aff" rid="aff29"><sup>29</sup></xref><xref ref-type="aff" rid="aff68"><sup>68</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vollenweider</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff99"><sup>99</sup></xref></contrib><contrib contrib-type="author"><name><surname>Raitakari</surname><given-names>Olli</given-names></name><xref ref-type="aff" rid="aff100"><sup>100</sup></xref></contrib><contrib contrib-type="author"><name><surname>Metspalu</surname><given-names>Andres</given-names></name><xref ref-type="aff" rid="aff44"><sup>44</sup></xref><xref ref-type="aff" rid="aff45"><sup>45</sup></xref></contrib><contrib contrib-type="author"><name><surname>Palmer</surname><given-names>Colin</given-names></name><xref ref-type="aff" rid="aff101"><sup>101</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gasparini</surname><given-names>Paolo</given-names></name><xref ref-type="aff" rid="aff92"><sup>92</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pirastu</surname><given-names>Mario</given-names></name><xref ref-type="aff" rid="aff49"><sup>49</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jukema</surname><given-names>J. Wouter</given-names></name><xref ref-type="aff" rid="aff50"><sup>50</sup></xref><xref ref-type="aff" rid="aff102"><sup>102</sup></xref><xref ref-type="aff" rid="aff103"><sup>103</sup></xref><xref ref-type="aff" rid="aff104"><sup>104</sup></xref></contrib><contrib contrib-type="author"><name><surname>Probst-Hensch</surname><given-names>Nicole M.</given-names></name><xref ref-type="aff" rid="aff51"><sup>51</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kronenberg</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="aff52"><sup>52</sup></xref></contrib><contrib contrib-type="author"><name><surname>Toniolo</surname><given-names>Daniela</given-names></name><xref ref-type="aff" rid="aff53"><sup>53</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gudnason</surname><given-names>Vilmundur</given-names></name><xref ref-type="aff" rid="aff23"><sup>23</sup></xref><xref ref-type="aff" rid="aff24"><sup>24</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shuldiner</surname><given-names>Alan R.</given-names></name><xref ref-type="aff" rid="aff25"><sup>25</sup></xref><xref ref-type="aff" rid="aff105"><sup>105</sup></xref></contrib><contrib contrib-type="author"><name><surname>Coresh</surname><given-names>Josef</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff106"><sup>106</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schmidt</surname><given-names>Reinhold</given-names></name><xref ref-type="aff" rid="aff57"><sup>57</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ferrucci</surname><given-names>Luigi</given-names></name><xref ref-type="aff" rid="aff27"><sup>27</sup></xref></contrib><contrib contrib-type="author"><name><surname>Siscovick</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M.</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>Borecki</surname><given-names>Ingrid</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kardia</surname><given-names>Sharon L. R.</given-names></name><xref ref-type="aff" rid="aff107"><sup>107</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yongmei</given-names></name><xref ref-type="aff" rid="aff31"><sup>31</sup></xref></contrib><contrib contrib-type="author"><name><surname>Curhan</surname><given-names>Gary C.</given-names></name><xref ref-type="aff" rid="aff108"><sup>108</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rudan</surname><given-names>Igor</given-names></name><xref ref-type="aff" rid="aff70"><sup>70</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gyllensten</surname><given-names>Ulf</given-names></name><xref ref-type="aff" rid="aff33"><sup>33</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>James F.</given-names></name><xref ref-type="aff" rid="aff70"><sup>70</sup></xref></contrib><contrib contrib-type="author"><name><surname>Franke</surname><given-names>Andre</given-names></name><xref ref-type="aff" rid="aff72"><sup>72</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pramstaller</surname><given-names>Peter P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rettig</surname><given-names>Rainer</given-names></name><xref ref-type="aff" rid="aff109"><sup>109</sup></xref></contrib><contrib contrib-type="author"><name><surname>Prokopenko</surname><given-names>Inga</given-names></name><xref ref-type="aff" rid="aff81"><sup>81</sup></xref></contrib><contrib contrib-type="author"><name><surname>Witteman</surname><given-names>Jacqueline C. M.</given-names></name><xref ref-type="aff" rid="aff36"><sup>36</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hayward</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="aff84"><sup>84</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ridker</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff48"><sup>48</sup></xref><xref ref-type="aff" rid="aff110"><sup>110</sup></xref></contrib><contrib contrib-type="author"><name><surname>Parsa</surname><given-names>Afshin</given-names></name><xref ref-type="aff" rid="aff111"><sup>111</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bochud</surname><given-names>Murielle</given-names></name><xref ref-type="aff" rid="aff112"><sup>112</sup></xref></contrib><contrib contrib-type="author"><name><surname>Heid</surname><given-names>Iris M.</given-names></name><xref ref-type="aff" rid="aff113"><sup>113</sup></xref><xref ref-type="aff" rid="aff114"><sup>114</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goessling</surname><given-names>Wolfram</given-names></name><xref ref-type="aff" rid="aff115"><sup>115</sup></xref><xref ref-type="aff" rid="aff116"><sup>116</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chasman</surname><given-names>Daniel I.</given-names></name><xref ref-type="aff" rid="aff48"><sup>48</sup></xref><xref ref-type="aff" rid="aff110"><sup>110</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kao</surname><given-names>W. H. Linda</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff106"><sup>106</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>Caroline S.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref><xref ref-type="aff" rid="aff117"><sup>117</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Institute of Genetic Medicine, European Academy of Bozen/Bolzano (EURAC) and Affiliated Institute of the University of Lübeck, Bolzano, Italy</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></aff><aff id="aff8"><label>8</label><addr-line>Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany</addr-line></aff><aff id="aff10"><label>10</label><addr-line>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff11"><label>11</label><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff12"><label>12</label><addr-line>Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, United States of America</addr-line></aff><aff id="aff13"><label>13</label><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></aff><aff id="aff14"><label>14</label><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff15"><label>15</label><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff16"><label>16</label><addr-line>Renal Division, Freiburg University Clinic, Freiburg, Germany</addr-line></aff><aff id="aff17"><label>17</label><addr-line>National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, United States of America</addr-line></aff><aff id="aff18"><label>18</label><addr-line>Division of Nephrology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff19"><label>19</label><addr-line>Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff20"><label>20</label><addr-line>Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></aff><aff id="aff21"><label>21</label><addr-line>Centre for Medical Systems Biology, Leiden, The Netherlands</addr-line></aff><aff id="aff22"><label>22</label><addr-line>Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff23"><label>23</label><addr-line>Icelandic Heart Association, Research Institute, Kopavogur, Iceland</addr-line></aff><aff id="aff24"><label>24</label><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></aff><aff id="aff25"><label>25</label><addr-line>Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff26"><label>26</label><addr-line>Department of Epidemiology and Biostatistics and Department of Forensic Molecular Biology, Erasmus University Medical Centre, Rotterdam, The Netherlands</addr-line></aff><aff id="aff27"><label>27</label><addr-line>Clinical Research Branch, National Institute of Aging, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff28"><label>28</label><addr-line>University of Washington, Seattle, Washington, United States of America</addr-line></aff><aff id="aff29"><label>29</label><addr-line>Department of Developmental Biology, Stanford University, Stanford, California, United States of America</addr-line></aff><aff id="aff30"><label>30</label><addr-line>Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></aff><aff id="aff31"><label>31</label><addr-line>Department of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></aff><aff id="aff32"><label>32</label><addr-line>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff33"><label>33</label><addr-line>Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden</addr-line></aff><aff id="aff34"><label>34</label><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></aff><aff id="aff35"><label>35</label><addr-line>IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany</addr-line></aff><aff id="aff36"><label>36</label><addr-line>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></aff><aff id="aff37"><label>37</label><addr-line>Inserm UMR744, Institut Pasteur, Lille, France</addr-line></aff><aff id="aff38"><label>38</label><addr-line>Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, Australia</addr-line></aff><aff id="aff39"><label>39</label><addr-line>Centre for Information-based Medicine, Hunter Medical Research Institute, Newcastle, Australia</addr-line></aff><aff id="aff40"><label>40</label><addr-line>Institute of Genetics and Biophysics “Adriano-Buzzati Traverso”–CNR, Napoli, Italy</addr-line></aff><aff id="aff41"><label>41</label><addr-line>Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland</addr-line></aff><aff id="aff42"><label>42</label><addr-line>Swiss Institute of Bioinformatics, Lausanne, Switzerland</addr-line></aff><aff id="aff43"><label>43</label><addr-line>Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Centre for Laboratory Medicine Tampere Finn-Medi 2, Tampere, Finland</addr-line></aff><aff id="aff44"><label>44</label><addr-line>Estonian Genome Center of University of Tartu (EGCUT), Tartu, Estonia</addr-line></aff><aff id="aff45"><label>45</label><addr-line>Estonian Biocenter and Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia</addr-line></aff><aff id="aff46"><label>46</label><addr-line>Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></aff><aff id="aff47"><label>47</label><addr-line>Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy</addr-line></aff><aff id="aff48"><label>48</label><addr-line>Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff49"><label>49</label><addr-line>Institute of Population Genetics – CNR, Sassari, Italy</addr-line></aff><aff id="aff50"><label>50</label><addr-line>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</addr-line></aff><aff id="aff51"><label>51</label><addr-line>Unit of Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland</addr-line></aff><aff id="aff52"><label>52</label><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></aff><aff id="aff53"><label>53</label><addr-line>Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy</addr-line></aff><aff id="aff54"><label>54</label><addr-line>Laboratory of Epidemiology, Demography, and Biometry, NIA, Bethesda, Maryland, United States of America</addr-line></aff><aff id="aff55"><label>55</label><addr-line>Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America</addr-line></aff><aff id="aff56"><label>56</label><addr-line>Austrian Stroke Prevention Study, Institute of Molecular Biology and Biochemistry and Department of Neurology, Medical University Graz, Graz, Austria</addr-line></aff><aff id="aff57"><label>57</label><addr-line>Austrian Stroke Prevention Study, University Clinic of Neurology, Department of Special Neurology, Medical University Graz, Graz, Austria</addr-line></aff><aff id="aff58"><label>58</label><addr-line>Division of Nephrology/Tufts Evidence Practice Center, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff59"><label>59</label><addr-line>Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States of America</addr-line></aff><aff id="aff60"><label>60</label><addr-line>Department of Internal Medicine/Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></aff><aff id="aff61"><label>61</label><addr-line>Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></aff><aff id="aff62"><label>62</label><addr-line>Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America</addr-line></aff><aff id="aff63"><label>63</label><addr-line>Abteilung Innere II, Universitätsklinikum Ulm, Ulm, Germany</addr-line></aff><aff id="aff64"><label>64</label><addr-line>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff65"><label>65</label><addr-line>Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany</addr-line></aff><aff id="aff66"><label>66</label><addr-line>Klinikum Grosshadern, Neuherberg, Germany</addr-line></aff><aff id="aff67"><label>67</label><addr-line>Croatian Centre for Global Health, University of Split Medical School, Split, Croatia</addr-line></aff><aff id="aff68"><label>68</label><addr-line>Department of Genetics, Stanford University, Stanford, California, United States of America</addr-line></aff><aff id="aff69"><label>69</label><addr-line>Department of Medicine, University of Chicago, Chicago, Illinois, United States of America</addr-line></aff><aff id="aff70"><label>70</label><addr-line>Center for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom</addr-line></aff><aff id="aff71"><label>71</label><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></aff><aff id="aff72"><label>72</label><addr-line>Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany</addr-line></aff><aff id="aff73"><label>73</label><addr-line>popgen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany</addr-line></aff><aff id="aff74"><label>74</label><addr-line>Clinic for Prosthodontic Dentistry, Gerostomatology, and Material Science, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff75"><label>75</label><addr-line>Institute of Anatomy and Cell Biology, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff76"><label>76</label><addr-line>Institute of Pharmacology, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff77"><label>77</label><addr-line>Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff78"><label>78</label><addr-line>Clinic for Internal Medicine A, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff79"><label>79</label><addr-line>Institute for Community Medicine, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff80"><label>80</label><addr-line>Department of Medicine, University of Leipzig, Leipzig, Germany</addr-line></aff><aff id="aff81"><label>81</label><addr-line>Wellcome Trust Centre for Human Genetics and Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom</addr-line></aff><aff id="aff82"><label>82</label><addr-line>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands</addr-line></aff><aff id="aff83"><label>83</label><addr-line>Croatian Centre for Global Health, Faculty of Medicine, University of Split, Split, Croatia</addr-line></aff><aff id="aff84"><label>84</label><addr-line>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom</addr-line></aff><aff id="aff85"><label>85</label><addr-line>INSERM U897, Université Victor Ségalen Bordeaux 2, ISPED, Bordeaux, France</addr-line></aff><aff id="aff86"><label>86</label><addr-line>Université Bordeaux 2 Victor Segalen, Bordeaux, France</addr-line></aff><aff id="aff87"><label>87</label><addr-line>Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia</addr-line></aff><aff id="aff88"><label>88</label><addr-line>Centre for Eye Research Australia (CERA), University of Melbourne, Melbourne, Australia</addr-line></aff><aff id="aff89"><label>89</label><addr-line>Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland</addr-line></aff><aff id="aff90"><label>90</label><addr-line>Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland</addr-line></aff><aff id="aff91"><label>91</label><addr-line>NHS Tayside, Wellcome Trust Centre for Molecular Medicine, Clinical Research Centre, Ninewells Hospital, University of Dundee, Dundee, United Kingdom</addr-line></aff><aff id="aff92"><label>92</label><addr-line>Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” University of Trieste, Trieste, Italy</addr-line></aff><aff id="aff93"><label>93</label><addr-line>University Medical Centre Mannheim, 5th Department of Medicine, Mannheim, Germany</addr-line></aff><aff id="aff94"><label>94</label><addr-line>Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom</addr-line></aff><aff id="aff95"><label>95</label><addr-line>Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</addr-line></aff><aff id="aff96"><label>96</label><addr-line>First Department of Internal Medicine, Paracelsus Medical University, Salzburg, Austria</addr-line></aff><aff id="aff97"><label>97</label><addr-line>Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria</addr-line></aff><aff id="aff98"><label>98</label><addr-line>Inserm UMRS 1018, CESP Team 10, Université Paris Sud, Villejuif, France</addr-line></aff><aff id="aff99"><label>99</label><addr-line>Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland</addr-line></aff><aff id="aff100"><label>100</label><addr-line>Research Centre of Applied and Preventive Cardiovascular Medicine, Department of Clinical Physiology, Turku University Hospital, University of Turku, Turku, Finland</addr-line></aff><aff id="aff101"><label>101</label><addr-line>Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom</addr-line></aff><aff id="aff102"><label>102</label><addr-line>Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands</addr-line></aff><aff id="aff103"><label>103</label><addr-line>Einthoven Laboratory for Experimental Vascular Medicine, Leiden, The Netherlands</addr-line></aff><aff id="aff104"><label>104</label><addr-line>Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</addr-line></aff><aff id="aff105"><label>105</label><addr-line>Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff106"><label>106</label><addr-line>Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff107"><label>107</label><addr-line>Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America</addr-line></aff><aff id="aff108"><label>108</label><addr-line>Brigham and Women's Hospital and Channing Laboratory, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff109"><label>109</label><addr-line>Institute of Physiology, University of Greifswald, Greifswald, Germany</addr-line></aff><aff id="aff110"><label>110</label><addr-line>Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff111"><label>111</label><addr-line>Division of Nephrology, University of Maryland Medical School, Baltimore, Maryland, United States of America</addr-line></aff><aff id="aff112"><label>112</label><addr-line>University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland</addr-line></aff><aff id="aff113"><label>113</label><addr-line>Department of Epidemiology and Preventive Medicine, University Hospital Regensburg, Regensburg, Germany</addr-line></aff><aff id="aff114"><label>114</label><addr-line>Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff115"><label>115</label><addr-line>Divisions of Genetics and Gastroenterology, Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America</addr-line></aff><aff id="aff116"><label>116</label><addr-line>Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, United States of America</addr-line></aff><aff id="aff117"><label>117</label><addr-line>Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Gibson</surname><given-names>Greg</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Georgia Institute of Technology, United States of America</aff><author-notes><corresp id="cor1">* E-mail: <email>foxca@nhlbi.nih.gov</email> (CSF); <email>wkao@jhsph.edu</email> (WHL Kao)</corresp><fn fn-type="con"><p>Study design: V Gudnason, TB Harris, LJ Launer, G Eiriksdottir, A Parsa, A Köttgen, WHL Kao, R Schmidt, L Ferrucci, DS Siscovick, BA Oostra, CM van Duijn, I Borecki, CS Fox, FB Hu, CA Böger, M Gorski, T Illig, A Döring, HE Wichmann, IM Heid, I Rudan, PP Pramstaller, GC Curhan, U Gyllensten, JF Wilson, SH Wild, AF Wright, H Campbell, A Hofman, AG Uitterlinden, JCM Witteman, R Biffar, K Endlich, R Rettig, S Stracke, H Völzke, P Kovacs, A Tönjes, O Polasek, N Hastie, C Hayward, V Vitart, DI Chasman, P Ridker, C Helmer, A Metspalu, JJ Wang, P Mitchell, M Province, X Gao, M Ciullo, P Vollenweider, M Pirastu, B Paulweber, D Toniolo, T Lehtimäki, O Raitakari, M Kähönen, J Viikari, P Gasparini, H Colhoun, A Doney, C Palmer, H Deshmukh, S Trompet, I Ford, BM Buckley, JW Jukema, NM Probst-Hensch. Study management: V Gudnason, TB Harris, LJ Launer, G Eiriksdottir, A Parsa, WHL Kao, R Schmidt, H Schmidt, M Cavalieri, L Ferrucci, DS Siscovick, A Isaacs, BA Oostra, CM van Duijn, I Borecki, CS Fox, J Ding, Y Liu, MC Cornelis, FB Hu, W Koenig, T Illig, A Döring, HE Wichmann, I Rudan, I Kolcic, T Zemunik, M Boban, C Pattaro, PP Pramstaller, GC Curhan, A Johansson, G Zaboli, U Gyllensten, JF Wilson, SH Wild, U Nöthlings, A Hofman, AG Uitterlinden, JCM Witteman, R Biffar, K Endlich, R Rettig, U Völker, H Völkze, M Stumvoll, A Tönjes, O Polasek, N Hastie, C Hayward, V Vitart, DI Chasman, P Ridker, C Helmer, A Metspalu, JJ Wang, P Mitchell, M Province, X Gao, M Ciullo, M Bochud, P Vollenweider, M Pirastu, B Kollerits, M Haun, B Paulweber, F Kronenberg, D Toniolo, T Lehtimäki, O Raitakari, M Kähönen, J Viikari, P Gasparini, F Giulianini, H Colhoun, A Doney, C Palmer, H Deshmukh, S Trompet, I Ford, BM Buckley, JW Jukema, BK Krämer, NM Probst-Hensch, M Imboden. Subject recruitment: G Eiriksdottir, AR Shuldiner, BD Mitchell, J Coresh, R Schmidt, M Cavalieri, DS Siscovick, BA Oostra, CM van Duijn, TB Harris, T Illig, A Döring, HE Wichmann, I Rudan, I Kolcic, PP Pramstaller, A Johansson, JF Wilson, SH Wild, A Hofman, AG Uitterlinden, JCM Witteman, R Biffar, R Rettig, S Stracke, H Völkze, A Tönjes, O Polasek, C Helmer, P Mitchell, M Ciullo, P Vollenweider, M Pirastu, B Paulweber, D Toniolo, O Raitakari, M Kähönen, J Viikari, S Ulivi, A Robino, P Ridker, H Colhoun, A Doney, C Palmer, I Ford, BM Buckley, JW Jukema, NM Probst-Hensch. Genotyping: AR Shuldiner, BD Mitchell, E Boerwinkle, H Schmidt, A Isaacs, A Demirkan, BA Oostra, CM van Duijn, M de Andrade, EJ Atkinson, ST Turner, SLR Kardia, Y Liu, CA Böger, M Gorski, T Illig, HE Wichmann, IM Heid, JF Wilson, H Campbell, A Franke, AG Uitterlinden, F Rivadeneira, F Ernst, G Homuth, HK Kroemer, M Nauck, U Völker, M Stumvoll, O Polasek, C Hayward, DI Chasman, T Esko, M Haun, F Kronenberg, T Lehtimäki, F Giulianini, S Trompet, JW Jukema. Statistical methods and analysis: T Aspelund, AV Smith, A Parsa, JR O'Connell, A Köttgen, WHL Kao, A Tin, C Hundertmark, M Struchalin, T Tanaka, G Li, A Isaacs, A Demirkan, M Feitosa, CS Fox, MH Chen, MC Foster, SJ Hwang, Q Yang, K Lohman, JS Andrews, Y Liu, MC Cornelis, CA Böger, M Gorski, IM Heid, C Pattaro, D Taliun, C Fuchsberger, C Minelli, A Johansson, W Igl, D Ellinghaus, A Franke, A Dehghan, F Rivadeneira, YS Aulchenko, A Teumer, I Prokopenko, R Mägi, C Hayward, V Vitart, DI Chasman, T Esko, EG Holliday, X Gao, S Ketkar, D Ruggiero, R Sorice, Z Kutalik, S Bergmann, F Murgia, L Portas, B Kollerits, F Kronenberg, G Pistis, S Ulivi, A Robino, AY Chu, H Colhoun, A Doney, C Palmer, H Deshmukh, I Ford, NM Probst-Hensch, M Adam, GA Thun, M Olden, M Li, N Glazer, HJ Gierman, V Chouraki, HE Wheeler, G Jacobs, T Nikopensius, M Metzger. Bioinformatics: AV Smith, JR O'Connell, C Hundertmark, M Struchalin, G Li, MH Chen, Q Yang, K Lohman, JS Andrews, Y Liu, MC Cornelis, CA Böger, M Gorski, IM Heid, C Pattaro, D Taliun, C Fuchsberger, A Johansson, W Igl, D Ellinghaus, A Dehghan, F Rivadeneira, YS Aulchenko, HK Kroemer, A Teumer, I Prokopenko, R Mägi, DI Chasman, T Esko, D Ruggiero, R Sorice, S Bergmann, F Murgia, L Portas, G Pistis, C Sala, T Lehtimäki, O Raitakari, S Ulivi, F Giulianini, S Trompet, I Ford, M Imboden, C-T Liu, AD Johnson, SK Kim. Zebrafish studies: M Garnaas, W Goessling. Interpretation of results: V Gudnason, TB Harris, LJ Launer, AV Smith, A Parsa, A Köttgen, WHL Kao, A Tin, DS Siscovick, G Li, M Rao, A Isaacs, MH Chen, MC Foster, SJ Hwang, Q Yang, J Ding, K Lohman, Y Liu, CA Böger, M Gorski, IM Heid, I Rudan, T Zemunik, M Boban, C Pattaro, D Taliun, A Johansson, W Igl, G Zaboli, U Gyllensten, JF Wilson, SH Wild, R Biffar, K Endlich, HK Kroemer, M Nauck, R Rettig, S Stracke, A Teumer, U Völker, H Völkze, O Polasek, N Hastie, C Hayward, V Vitart, DI Chasman, BI Freedman, T Esko, A Metspalu, EG Holliday, I Borecki, M Province, X Gao, M Ciullo, M Bochud, B Kollerits, M Haun, B Paulweber, F Kronenberg, D Toniolo, G Pistis, C Sala, AY Chu, S Trompet, JW Jukema, M Garnaas, W Goessling, CS Fox. Wrote the manuscript: C Pattaro, A Köttgen, A Teumer, M Garnaas, CA Böger, C Fuchsberger, A Tin, CM O'Seaghdha, A Parsa, M Bochud, IM Heid, W Goessling, DI Chasman, WHL Kao, CS Fox.</p></fn><fn id="fn1" fn-type="other"><p>¶ These authors were joint senior authors on this work.</p></fn></author-notes><pub-date pub-type="collection"><month>3</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>29</day><month>3</month><year>2012</year></pub-date><pub-date pub-type="ecorrected"><day>02
</day><month>4</month><year>2012</year></pub-date><volume>8</volume><issue>3</issue><elocation-id>e1002584</elocation-id><history><date date-type="received"><day>1</day><month>10</month><year>2011</year></date><date date-type="accepted"><day>22</day><month>1</month><year>2012</year></date></history><permissions><copyright-statement>Pattaro et al.</copyright-statement><copyright-year>2012</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near <italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>SLC47A1</italic>, <italic>CDK12</italic>, <italic>CASP9</italic>, and <italic>INO80</italic>. Morpholino knockdown of <italic>mpped2</italic> and <italic>casp9</italic> in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Chronic kidney disease (CKD) is an important public health problem with a hereditary component. We performed a new genome-wide association study in up to 130,600 European ancestry individuals to identify genes that may influence kidney function, specifically genes that may influence kidney function differently depending on sex, age, hypertension, and diabetes status of individuals. We uncovered 6 new loci associated with estimated glomerular filtration rate (eGFR), the primary measure of renal function, in or near <italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>SLC47A1</italic>, <italic>CDK12</italic>, <italic>CASP9</italic>, and <italic>INO80</italic>. <italic>CDK12</italic> effect was stronger in younger and absent in older individuals. <italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>SLC47A1</italic>, and <italic>CDK12</italic> loci were associated with eGFR in African ancestry samples as well, highlighting the cross-ethnicity validity of our findings. Using the zebrafish model, we performed morpholino knockdown of <italic>mpped2</italic> and <italic>casp9</italic> in zebrafish embryos and revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. These results further our understanding of the pathogenesis of CKD and provide insights into potential novel mechanisms of disease.</p></abstract><counts><page-count count="15"></page-count></counts></article-meta></front><body><sec id="s1"><title>Introduction</title><p>Chronic kidney disease (CKD) affects nearly 10% of the global population <xref rid="pgen.1002584-MeguidElNahas1" ref-type="bibr">[1]</xref>, <xref rid="pgen.1002584-Imai1" ref-type="bibr">[2]</xref>, and its prevalence continues to increase <xref rid="pgen.1002584-Coresh1" ref-type="bibr">[3]</xref>. Reduced estimated glomerular filtration rate (eGFR), the primary measure used to define CKD (eGFR<60 ml/min/1.73 m<sup>2</sup>) <xref rid="pgen.1002584-Levey1" ref-type="bibr">[4]</xref>, is associated with an increased risk of cardiovascular morbidity and mortality <xref rid="pgen.1002584-vanderVelde1" ref-type="bibr">[5]</xref>, acute kidney injury <xref rid="pgen.1002584-Gansevoort1" ref-type="bibr">[6]</xref>, and end stage renal disease (ESRD) <xref rid="pgen.1002584-Gansevoort1" ref-type="bibr">[6]</xref>, <xref rid="pgen.1002584-Astor1" ref-type="bibr">[7]</xref>.</p><p>Using genome-wide association studies (GWAS) in predominantly population-based cohorts, we and others have previously identified more than 20 genetic loci associated with eGFR and CKD <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>–<xref rid="pgen.1002584-Gudbjartsson1" ref-type="bibr">[11]</xref>. Although most of these genetic effects seem largely robust across strata of diabetes or hypertension status <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref>, evidence suggests that some of the loci such as the <italic>UMOD</italic> locus may have heterogeneous effects across these strata <xref rid="pgen.1002584-Gudbjartsson1" ref-type="bibr">[11]</xref>. We thus hypothesized that GWAS in study populations stratified by four key CKD risk factors - age, sex, diabetes or hypertension status - may permit the identification of novel eGFR and CKD loci. We carried this out by extending our previous work <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref> to a larger discovery sample of 74,354 individuals with independent replication in additional 56,246 individuals, resulting in a total of 130,600 individuals of European ancestry. To assess for potential heterogeneity, we performed separate genome-wide association analyses across strata of CKD risk factors, as well as in a more extreme CKD phenotype.</p></sec><sec id="s2"><title>Results</title><p>Meta-analyses of GWAS on the 22 autosomes were performed for: 1) eGFR based on serum creatinine (eGFRcrea) and CKD (6,271 cases) in the overall sample, 2) eGFRcrea and CKD stratified by the four risk factors, and 3) CKD45, a more severe CKD phenotype defined as eGFRcrea <45 ml/min/1.73 m<sup>2</sup> in the overall sample (2,181 cases). For the stratified analyses, in addition to identifying loci that were significant within each stratum, we performed a genome-wide comparison of the effect estimates between strata of the four risk factors. A complete overview of the analysis workflow is given in <xref ref-type="supplementary-material" rid="pgen.1002584.s001">Figure S1</xref>. All studies participating in the stage 1 discovery and stage 2 replication phases are listed in <xref ref-type="supplementary-material" rid="pgen.1002584.s013">Tables S1</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s014">S2</xref>. The characteristics of all stage 1 discovery samples by study are reported in <xref ref-type="supplementary-material" rid="pgen.1002584.s015">Table S3</xref>, and information on study design and genotyping are reported in <xref ref-type="supplementary-material" rid="pgen.1002584.s016">Table S4</xref>. Results of the eGFRcrea analyses are summarized in the Manhattan and quantile-quantile plots reported in <xref ref-type="supplementary-material" rid="pgen.1002584.s002">Figures S2</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s003">S3</xref>. A total of 21 SNPs from the discovery stage were carried forward for replication in an independent set of 56,246 individuals (<xref ref-type="supplementary-material" rid="pgen.1002584.s017">Tables S5</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s018">S6</xref>). These SNPs were selected for replication for the following (<xref ref-type="supplementary-material" rid="pgen.1002584.s001">Figure S1</xref>): 5 reached genome-wide significance in either eGFRcrea overall or stratified analyses, 1 based on a test of direction-consistency of SNP-eGFR associations across the discovery cohorts for eGFRcrea overall, 4 demonstrated a <italic>P</italic> value≤10<sup>−6</sup> and high between-study homogeneity (I<sup>2</sup><25%) in the CKD45 analysis (<xref ref-type="supplementary-material" rid="pgen.1002584.s019">Table S7</xref>), and 11 demonstrated between-strata <italic>P</italic> value≤5×10<sup>−5</sup> along with a <italic>P</italic> value≤5×10<sup>−5</sup> for association with eGFRcrea in at least one of the two strata (<xref ref-type="supplementary-material" rid="pgen.1002584.s020">Table S8</xref>).</p><p>While none of the loci identified for CKD45 or the test for between-strata difference analyses replicated, all 6 loci identified from the eGFRcrea overall analysis, stratified analyses, and the direction test did (<xref ref-type="table" rid="pgen-1002584-t001">Table 1</xref>). These 6 loci were identified and replicated in the overall analysis (rs3925584, located upstream of the <italic>MPPED2</italic> gene; rs6431731 near the <italic>DDX1</italic> gene), in the diabetes-free sub-group (rs2453580 in an intron of the <italic>SLC47A1</italic> gene), in the younger age stratum (rs11078903 in an intron of the <italic>CDK12</italic> gene; rs12124078 located near the <italic>CASP9</italic> gene), and the direction test (rs2928148, located in the <italic>INO80</italic> gene, see Methods for details). In the combined meta-analysis of all 45 studies used in the discovery and replication stages, all six SNPs met the genome-wide significance threshold of 5×10<sup>−8</sup>, with individual <italic>P</italic> values ranging from 4.3×10<sup>−8</sup> to 8.4×10<sup>−18</sup> (<xref ref-type="table" rid="pgen-1002584-t001">Table 1</xref>). The imputation quality of these SNPs is reported in <xref ref-type="supplementary-material" rid="pgen.1002584.s021">Table S9</xref>, and <xref ref-type="supplementary-material" rid="pgen.1002584.s004">Figure S4</xref> shows the regional association plots for each of the 6 loci. We also confirmed all previously identified renal function loci in the current data (<xref ref-type="supplementary-material" rid="pgen.1002584.s022">Table S10</xref>). Brief descriptions of the genes included within the 6 new loci uncovered can be found in <xref ref-type="supplementary-material" rid="pgen.1002584.s023">Table S11</xref>. Forest plots for the associations between the index SNP at each of the 6 novel loci and eGFR across all discovery studies and all strata are presented in <xref ref-type="supplementary-material" rid="pgen.1002584.s005">Figures S5</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s006">S6</xref>. Most of the 6 new loci had similar associations across strata of CKD risk factors except for the <italic>CDK12</italic> locus, which revealed stronger association in the younger (≤65 years of age) as compared to the older age group (>65 years of age).</p><table-wrap id="pgen-1002584-t001" position="float"><object-id pub-id-type="doi">10.1371/journal.pgen.1002584.t001</object-id><label>Table 1</label><caption><title>Novel loci associated with eGFRcrea.</title></caption><alternatives><graphic id="pgen-1002584-t001-1" xlink:href="pgen.1002584.t001"></graphic><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col></colgroup><thead><tr><td colspan="6" align="left" rowspan="1">Locus description</td><td colspan="2" align="left" rowspan="1">Discovery analysis</td><td colspan="3" align="left" rowspan="1">Replication analysis</td><td colspan="3" align="left" rowspan="1">Combined analysis<xref ref-type="table-fn" rid="nt107">†</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">Analysis subgroup</td><td align="left" rowspan="1" colspan="1">SNP ID</td><td align="left" rowspan="1" colspan="1">Chr</td><td align="left" rowspan="1" colspan="1">Position (bp)<xref ref-type="table-fn" rid="nt103">‡</xref></td><td align="left" rowspan="1" colspan="1">Genes nearby<xref ref-type="table-fn" rid="nt103">‡</xref></td><td align="left" rowspan="1" colspan="1">Ref./Non-Ref. alleles (RAF)</td><td align="left" rowspan="1" colspan="1">Effect(SE)<xref ref-type="table-fn" rid="nt104">§</xref></td><td align="left" rowspan="1" colspan="1"><italic>P</italic> value<xref ref-type="table-fn" rid="nt104">§</xref></td><td align="left" rowspan="1" colspan="1">Effect(SE)</td><td align="left" rowspan="1" colspan="1">1-sided <italic>P</italic> value</td><td align="left" rowspan="1" colspan="1">Q value</td><td align="left" rowspan="1" colspan="1">Effect(SE)</td><td align="left" rowspan="1" colspan="1"><italic>P</italic> value</td><td align="left" rowspan="1" colspan="1">I<sup>2</sup></td></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Overall</td><td align="left" rowspan="1" colspan="1">rs3925584</td><td align="left" rowspan="1" colspan="1">11</td><td align="left" rowspan="1" colspan="1">30,716,911</td><td align="left" rowspan="1" colspan="1"><italic>MPPED2</italic></td><td align="left" rowspan="1" colspan="1">T/C(0.54)</td><td align="left" rowspan="1" colspan="1">−0.0077(0.0013)</td><td align="left" rowspan="1" colspan="1">1.0×10<sup>−09</sup></td><td align="left" rowspan="1" colspan="1">−0.0073(0.0013)</td><td align="left" rowspan="1" colspan="1">4.0×10<sup>−9</sup></td><td align="left" rowspan="1" colspan="1">1.1×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">−0.0075(0.0009)</td><td align="left" rowspan="1" colspan="1">8.4×10<sup>−18</sup></td><td align="left" rowspan="1" colspan="1">21%</td></tr><tr><td align="left" rowspan="1" colspan="1">Overall</td><td align="left" rowspan="1" colspan="1">rs6431731</td><td align="left" rowspan="1" colspan="1">2</td><td align="left" rowspan="1" colspan="1">15,780,453</td><td align="left" rowspan="1" colspan="1"><italic>DDX1</italic></td><td align="left" rowspan="1" colspan="1">T/C(0.94)</td><td align="left" rowspan="1" colspan="1">−0.0181(0.0033)</td><td align="left" rowspan="1" colspan="1">4.6×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">−0.0065(0.0034)</td><td align="left" rowspan="1" colspan="1">0.0277</td><td align="left" rowspan="1" colspan="1">0.0195</td><td align="left" rowspan="1" colspan="1">−0.0127(0.0023)</td><td align="left" rowspan="1" colspan="1">4.3×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">11%</td></tr><tr><td align="left" rowspan="1" colspan="1">No Diabetes</td><td align="left" rowspan="1" colspan="1">rs2453580</td><td align="left" rowspan="1" colspan="1">17</td><td align="left" rowspan="1" colspan="1">19,378,913</td><td align="left" rowspan="1" colspan="1"><bold><italic>SLC47A1</italic></bold></td><td align="left" rowspan="1" colspan="1">T/C(0.59)</td><td align="left" rowspan="1" colspan="1">0.0076(0.0014)</td><td align="left" rowspan="1" colspan="1">4.6×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">0.0038(0.0014)</td><td align="left" rowspan="1" colspan="1">0.0037</td><td align="left" rowspan="1" colspan="1">0.0039</td><td align="left" rowspan="1" colspan="1">0.0059(0.0010)</td><td align="left" rowspan="1" colspan="1">2.1×10<sup>−09</sup></td><td align="left" rowspan="1" colspan="1">21%</td></tr><tr><td align="left" rowspan="1" colspan="1">Age≤65 yrs<xref ref-type="table-fn" rid="nt105">*</xref></td><td align="left" rowspan="1" colspan="1">rs12124078</td><td align="left" rowspan="1" colspan="1">1</td><td align="left" rowspan="1" colspan="1">15,742,486</td><td align="left" rowspan="1" colspan="1"><bold><italic>DNAJC16</italic></bold>, <italic>CASP9</italic>, <italic>AGMAT</italic></td><td align="left" rowspan="1" colspan="1">A/G(0.70)</td><td align="left" rowspan="1" colspan="1">0.0096(0.0015)</td><td align="left" rowspan="1" colspan="1">9.8×10<sup>−10</sup></td><td align="left" rowspan="1" colspan="1">0.0098(0.0017)</td><td align="left" rowspan="1" colspan="1">5.0×10<sup>−9</sup></td><td align="left" rowspan="1" colspan="1">1.1×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">0.0097(0.0011)</td><td align="left" rowspan="1" colspan="1">1.5×10<sup>−17</sup></td><td align="left" rowspan="1" colspan="1">20%</td></tr><tr><td align="left" rowspan="1" colspan="1">Age≤65 yrs</td><td align="left" rowspan="1" colspan="1">rs11078903</td><td align="left" rowspan="1" colspan="1">17</td><td align="left" rowspan="1" colspan="1">34,885,450</td><td align="left" rowspan="1" colspan="1"><bold><italic>CDK12</italic></bold>, <italic>MED1</italic>, <italic>FBXL20</italic></td><td align="left" rowspan="1" colspan="1">A/G(0.76)</td><td align="left" rowspan="1" colspan="1">−0.0103(0.0017)</td><td align="left" rowspan="1" colspan="1">2.4×10<sup>−09</sup></td><td align="left" rowspan="1" colspan="1">−0.0083(0.0023)</td><td align="left" rowspan="1" colspan="1">1.4×10<sup>−4</sup></td><td align="left" rowspan="1" colspan="1">2.0×10<sup>−04</sup></td><td align="left" rowspan="1" colspan="1">−0.0096(0.0013)</td><td align="left" rowspan="1" colspan="1">9.0×10<sup>−13</sup></td><td align="left" rowspan="1" colspan="1">0%</td></tr><tr><td align="left" rowspan="1" colspan="1">Direction Test (Overall)<xref ref-type="table-fn" rid="nt106">**</xref></td><td align="left" rowspan="1" colspan="1">rs2928148</td><td align="left" rowspan="1" colspan="1">15</td><td align="left" rowspan="1" colspan="1">39,188,842</td><td align="left" rowspan="1" colspan="1"><bold><italic>INO80</italic></bold>, <italic>EXD1</italic>, <italic>CHAC1</italic></td><td align="left" rowspan="1" colspan="1">A/G(0.52)</td><td align="left" rowspan="1" colspan="1">0.0064(0.0012)</td><td align="left" rowspan="1" colspan="1">1.2×10<sup>−07</sup></td><td align="left" rowspan="1" colspan="1">0.0033(0.0015)</td><td align="left" rowspan="1" colspan="1">0.0145</td><td align="left" rowspan="1" colspan="1">0.0122</td><td align="left" rowspan="1" colspan="1">0.0051(0.0009)</td><td align="left" rowspan="1" colspan="1">4.0×10<sup>−08</sup></td><td align="left" rowspan="1" colspan="1">0%</td></tr></tbody></table></alternatives><table-wrap-foot><fn id="nt101"><label></label><p>SNPs are listed in the stratum where the smallest <italic>P</italic> value in the discovery analysis was observed. Sample size/number of studies in the discovery phase: 74,354/26 (overall, direction test), 66,931/24 (No Diabetes), 46,435/23 (age ≤65 years); replication phase: 56,246/19 (overall, direction test), 41,218/17 (No Diabetes), 28,631/16 (age ≤65 years); combined analysis: 130,600/45 (overall, direction test), 108,149/41 (No Diabetes), 75,066/39 (age ≤65 years).</p></fn><fn id="nt102"><label></label><p>Chr.: chromosome; bp: base-pairs; Ref./Non-Ref. All.: reference/non-reference alleles; RAF: reference allele frequency; SE: standard error.</p></fn><fn id="nt103"><label>‡</label><p>Genes nearby were based on RefSeq genes (build 36). The gene closest to the SNP is listed first and is in boldface if the SNP is located within the gene.</p></fn><fn id="nt104"><label>§</label><p>Effects on log(eGFRcrea); post GWAS meta-analysis genomic control correction applied to <italic>P</italic> values and SEs.</p></fn><fn id="nt105"><label>*</label><p>While being uncovered in the younger samples, this locus showed consistent results in the non-diabetic group (combined-analysis <italic>P</italic> value 5.7×10<sup>−16</sup>) and in the overall population (<italic>P</italic> value 9.5×10<sup>−22</sup>) - see <xref ref-type="supplementary-material" rid="pgen.1002584.s028">Tables S16</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s022">S10</xref> for additional details.</p></fn><fn id="nt106"><label>**</label><p>The direction test was performed in the overall dataset; the genomic control corrected <italic>P</italic> value from the direction test for the SNP rs2928148 was 4.0×10<sup>−7</sup>. In the combined analysis, the largest effect size (0.0054 on log eGFR in ml/min/1.73 m<sup>2</sup>) and the smallest <italic>P</italic> value (3.7×10<sup>−8</sup>) were observed in the non-diabetic group.</p></fn><fn id="nt107"><label>†</label><p>All results were confirmed by random-effect meta-analysis.</p></fn></table-wrap-foot></table-wrap><p>We further examined our findings in 8,110 African ancestry participants from the CARe consortium <xref rid="pgen.1002584-Liu1" ref-type="bibr">[12]</xref> (<xref ref-type="table" rid="pgen-1002584-t002">Table 2</xref>). Not surprisingly, given linkage disequilibrium (LD) differences between Europeans and African Americans, none of the 6 lead SNPs uncovered in CKDGen achieved significance in the African American samples. Next, we interrogated the 250 kb flanking regions from the lead SNP at each locus, and showed that 4 of the 6 regions (<italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>SLC47A1</italic>, and <italic>CDK12</italic>) harbored SNPs that achieved statistical significance after correcting for multiple comparisons based on the genetic structure of each region (see Methods for details). <xref ref-type="fig" rid="pgen-1002584-g001">Figure 1</xref> presents the regional association plots for <italic>MPPED2</italic>, and <xref ref-type="supplementary-material" rid="pgen.1002584.s007">Figure S7</xref> presents the plots of the remaining loci in the African American sample. Imputation scores for the lead SNPs can be found in <xref ref-type="supplementary-material" rid="pgen.1002584.s024">Table S12</xref>. We observed that rs12278026, upstream of <italic>MPPED2</italic>, was associated with eGFRcrea in African Americans (<italic>P</italic> value = 5×10<sup>−5</sup>, threshold for statistical significance: <italic>P</italic> value = 0.001). While rs12278026 is monomorphic in the CEU population in HapMap, rs3925584 and rs12278026 have a D′ of 1 (r<sup>2</sup> = 0.005) in the YRI population, suggesting that these SNPs may have arisen from the same ancestral haplotype.</p><fig id="pgen-1002584-g001" position="float"><object-id pub-id-type="doi">10.1371/journal.pgen.1002584.g001</object-id><label>Figure 1</label><caption><title>Genetic association and LD distribution of the <italic>MPPED2</italic> gene locus in European and African ancestry populations.</title><p>Regional association plots in the CKDGen European ancestry discovery analysis (N = 74,354) (A) and in the CARe African ancestry discovery analysis (N = 8,110) (B). LD structure: comparison between the HapMap release II – CEU and YRI samples in the region included within +/−100 kb from the target SNP rs3925584 identified in the CKDGen GWAS. The green circle highlights a stream of high LD connecting the two blocks, indicating the presence of common haplotypes (C).</p></caption><graphic xlink:href="pgen.1002584.g001"></graphic></fig><table-wrap id="pgen-1002584-t002" position="float"><object-id pub-id-type="doi">10.1371/journal.pgen.1002584.t002</object-id><label>Table 2</label><caption><title>Interrogation of the six novel loci uncovered in the European ancestry (EA) individuals (CKDGen consortium) in individuals of African ancestry (AA) from the CARe consortium for the trait eGFRcrea.</title></caption><alternatives><graphic id="pgen-1002584-t002-2" xlink:href="pgen.1002584.t002"></graphic><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col><col align="center" span="1"></col></colgroup><thead><tr><td colspan="5" align="left" rowspan="1">Results for the lead SNPs in the CARe AA individuals</td><td colspan="8" align="left" rowspan="1">Best SNP in region in the CARe AA individuals</td></tr><tr><td align="left" rowspan="1" colspan="1">SNP ID<xref ref-type="table-fn" rid="nt109">*</xref></td><td align="left" rowspan="1" colspan="1">Nearby genes<xref ref-type="table-fn" rid="nt110">§</xref></td><td align="left" rowspan="1" colspan="1">Ref./Non-Ref. alleles (RAF)</td><td align="left" rowspan="1" colspan="1">Effect(SE)</td><td align="left" rowspan="1" colspan="1"><italic>P</italic> value</td><td align="left" rowspan="1" colspan="1">SNP ID</td><td align="left" rowspan="1" colspan="1">Position (build 36)</td><td align="left" rowspan="1" colspan="1">LD (R<sup>2</sup>) with lead SNP</td><td align="left" rowspan="1" colspan="1">RAF (Ref./Non-Ref. alleles)</td><td align="left" rowspan="1" colspan="1">Effect(SE)</td><td align="left" rowspan="1" colspan="1"><italic>P</italic> value</td><td align="left" rowspan="1" colspan="1">S<xref ref-type="table-fn" rid="nt111">**</xref></td><td align="left" rowspan="1" colspan="1">Bonferroni <italic>P</italic> value threshold (0.05/S)</td></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">rs3925584</td><td align="left" rowspan="1" colspan="1"><italic>MPPED2</italic></td><td align="left" rowspan="1" colspan="1">T/C (0.88)</td><td align="left" rowspan="1" colspan="1">−0.0005(0.0066)</td><td align="left" rowspan="1" colspan="1">0.9349</td><td align="left" rowspan="1" colspan="1">rs12278026</td><td align="left" rowspan="1" colspan="1">30,744,460</td><td align="left" rowspan="1" colspan="1">0.005</td><td align="left" rowspan="1" colspan="1">0.89 (A/G)</td><td align="left" rowspan="1" colspan="1">0.0342(0.0084)</td><td align="left" rowspan="1" colspan="1">4.6×10<sup>−5</sup></td><td align="left" rowspan="1" colspan="1">46</td><td align="left" rowspan="1" colspan="1">0.0011</td></tr><tr><td align="left" rowspan="1" colspan="1">rs6431731</td><td align="left" rowspan="1" colspan="1"><italic>DDX1</italic></td><td align="left" rowspan="1" colspan="1">T/C (0.99)</td><td align="left" rowspan="1" colspan="1">−0.0181(0.0213)</td><td align="left" rowspan="1" colspan="1">0.3948</td><td align="left" rowspan="1" colspan="1">rs4669002</td><td align="left" rowspan="1" colspan="1">15,874,859</td><td align="left" rowspan="1" colspan="1">NA<xref ref-type="table-fn" rid="nt112">†</xref></td><td align="left" rowspan="1" colspan="1">0.56 (T/C)</td><td align="left" rowspan="1" colspan="1">−0.0196(0.0047)</td><td align="left" rowspan="1" colspan="1">2.6×10<sup>−5</sup></td><td align="left" rowspan="1" colspan="1">78</td><td align="left" rowspan="1" colspan="1">6.4×10<sup>−4</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">rs12124078</td><td align="left" rowspan="1" colspan="1"><bold><italic>SLC47A1</italic></bold></td><td align="left" rowspan="1" colspan="1">A/G (0.69)</td><td align="left" rowspan="1" colspan="1">−0.0024(0.0045)</td><td align="left" rowspan="1" colspan="1">0.5956</td><td align="left" rowspan="1" colspan="1">rs1472554</td><td align="left" rowspan="1" colspan="1">15,987,920</td><td align="left" rowspan="1" colspan="1">0.004</td><td align="left" rowspan="1" colspan="1">0.50 (C/G)</td><td align="left" rowspan="1" colspan="1">−0.0120(0.0041)</td><td align="left" rowspan="1" colspan="1">0.0035</td><td align="left" rowspan="1" colspan="1">44</td><td align="left" rowspan="1" colspan="1">0.0011</td></tr><tr><td align="left" rowspan="1" colspan="1">rs2453580</td><td align="left" rowspan="1" colspan="1"><bold><italic>DNAJC16</italic></bold>, <italic>CASP9</italic>, <italic>AGMAT</italic></td><td align="left" rowspan="1" colspan="1">T/C (0.59)</td><td align="left" rowspan="1" colspan="1">0.0056(0.0049)</td><td align="left" rowspan="1" colspan="1">0.2524</td><td align="left" rowspan="1" colspan="1">rs1800869</td><td align="left" rowspan="1" colspan="1">19,505,226</td><td align="left" rowspan="1" colspan="1">0.011</td><td align="left" rowspan="1" colspan="1">0.93 (C/G)</td><td align="left" rowspan="1" colspan="1">−0.0294(0.0082)</td><td align="left" rowspan="1" colspan="1">3.6×10<sup>−4</sup></td><td align="left" rowspan="1" colspan="1">33</td><td align="left" rowspan="1" colspan="1">0.0015</td></tr><tr><td align="left" rowspan="1" colspan="1">rs11078903<xref ref-type="table-fn" rid="nt113">‡</xref></td><td align="left" rowspan="1" colspan="1"><bold><italic>CDK12</italic></bold>, <italic>MED1</italic>, <italic>FBXL20</italic></td><td align="left" rowspan="1" colspan="1">A/G (NA<xref ref-type="table-fn" rid="nt113">‡</xref>)</td><td align="left" rowspan="1" colspan="1">NA<xref ref-type="table-fn" rid="nt113">‡</xref></td><td align="left" rowspan="1" colspan="1">NA<xref ref-type="table-fn" rid="nt113">‡</xref></td><td align="left" rowspan="1" colspan="1">rs1874226</td><td align="left" rowspan="1" colspan="1">34,982,557</td><td align="left" rowspan="1" colspan="1">0.112</td><td align="left" rowspan="1" colspan="1">0.34 (T/C)</td><td align="left" rowspan="1" colspan="1">0.0157(0.0045)</td><td align="left" rowspan="1" colspan="1">4.2×10<sup>−4</sup></td><td align="left" rowspan="1" colspan="1">15</td><td align="left" rowspan="1" colspan="1">0.0033</td></tr><tr><td align="left" rowspan="1" colspan="1">rs2928148</td><td align="left" rowspan="1" colspan="1"><bold><italic>INO80</italic></bold>, <italic>EXD1</italic>, <italic>CHAC1</italic></td><td align="left" rowspan="1" colspan="1">A/G (0.22)</td><td align="left" rowspan="1" colspan="1">−0.0003(0.0053)</td><td align="left" rowspan="1" colspan="1">0.9497</td><td align="left" rowspan="1" colspan="1">rs8039934</td><td align="left" rowspan="1" colspan="1">39,284,719</td><td align="left" rowspan="1" colspan="1">0.105</td><td align="left" rowspan="1" colspan="1">0.50 (T/C)</td><td align="left" rowspan="1" colspan="1">−0.0086(0.0042)</td><td align="left" rowspan="1" colspan="1">0.0412</td><td align="left" rowspan="1" colspan="1">22</td><td align="left" rowspan="1" colspan="1">0.0023</td></tr></tbody></table></alternatives><table-wrap-foot><fn id="nt108"><label></label><p>Ref./Non-Ref. All.: reference/non-reference alleles; RAF: reference allele frequency; SE: standard error.</p></fn><fn id="nt109"><label>*</label><p>Characteristics of the six lead SNPs in the EA individuals from the CKDGen consortium can be found in <xref ref-type="table" rid="pgen-1002584-t001">Table 1</xref>.</p></fn><fn id="nt110"><label>§</label><p>The gene closest to the SNP is listed first and is in boldface if the SNP is located within the gene.</p></fn><fn id="nt111"><label>**</label><p>S = number of independent, typed SNPs interrogated.</p></fn><fn id="nt112"><label>†</label><p>No LD information available in the HapMap database between the target SNP and the best SNP in the DDX1 region.</p></fn><fn id="nt113"><label>‡</label><p>The SNP rs11078903 was not present in the CARe consortium database.</p></fn></table-wrap-foot></table-wrap><p>We also performed eQTL analyses of our 6 newly identified loci using known databases and a newly created renal eSNP database (see Methods) and found that rs12124078 was associated with <italic>cis</italic> expression of the nearby <italic>CASP9</italic> gene in myocytes, which encodes caspase-9, the third apoptotic activation factor involved in the activation of cell apoptosis, necrosis and inflammation (<italic>P</italic> value for the monocyte eSNP of interest = 3.7×10<sup>−13</sup>). In the kidney, caspase-9 may play an important role in the medulla response to hyperosmotic stress <xref rid="pgen.1002584-Allan1" ref-type="bibr">[13]</xref> and in cadmium-induced toxicity <xref rid="pgen.1002584-Gobe1" ref-type="bibr">[14]</xref>. The other 5 SNPs were not associated with any investigated eQTL. Additional eQTL analyses of 81 kidney biopsies (<xref ref-type="supplementary-material" rid="pgen.1002584.s025">Table S13</xref>) did not reveal further evidence of association with eQTLs (<xref ref-type="supplementary-material" rid="pgen.1002584.s026">Table S14</xref>).</p><p>Of the 6 novel loci identified, 2 (<italic>MPPED2</italic> and <italic>DDX1</italic>) were in regions containing only a single gene, and 1 (<italic>CASP9</italic>) had its expression associated with the locus lead SNP. Thus, to determine the potential involvement of these three genes during zebrafish kidney development, we independently assessed the expression of 4 well-characterized renal markers following morpholino knockdown: <italic>pax2a</italic> (global kidney) <xref rid="pgen.1002584-Drummond1" ref-type="bibr">[15]</xref>, <italic>nephrin</italic> (podocyte) <xref rid="pgen.1002584-KramerZucker1" ref-type="bibr">[16]</xref>, <italic>slc20a1a</italic> (proximal tubule) <xref rid="pgen.1002584-Wingert1" ref-type="bibr">[17]</xref>, and <italic>slc12a3</italic> (distal tubule) <xref rid="pgen.1002584-Wingert1" ref-type="bibr">[17]</xref>. While we observed no abnormalities in <italic>ddx1</italic> morphants (<xref ref-type="supplementary-material" rid="pgen.1002584.s008">Figure S8</xref>), <italic>mpped2</italic> and <italic>casp9</italic> knockdown resulted in expanded <italic>pax2a</italic> expression in the glomerular region in 90% and 75% of morphant embryos, respectively, compared to 0% in controls (<italic>P</italic> value<0.0001 for both genes; <xref ref-type="fig" rid="pgen-1002584-g002">Figure 2A</xref> versus 2F and 2K; 2B versus 2G and 2L; and 2P). Significant differences were also observed in expression of the podocyte marker <italic>nephrin</italic> (<xref ref-type="fig" rid="pgen-1002584-g002">Figure 2C versus 2H and 2M</xref>; 80% and 74% abnormalities for <italic>mpped2</italic> and <italic>casp9</italic>, respectively, versus 0% in controls, <italic>P</italic> value<0.0001 for both genes). For <italic>mpped2</italic>, no differences were observed in expression of the proximal or distal tubular markers <italic>slc20a1a</italic> and <italic>slc12a3</italic> (<italic>P</italic> value = 1.0; <xref ref-type="fig" rid="pgen-1002584-g002">Figure 2D versus 2I and 2E versus 2J</xref>). <italic>Casp9</italic> morphants and controls showed no differences in proximal tubular marker expression (<xref ref-type="fig" rid="pgen-1002584-g002">Figure 2D versus 2N</xref>), but abnormalities were observed in distal tubular marker expression in <italic>casp9</italic> knockdown embryos (30% versus 0%; <xref ref-type="fig" rid="pgen-1002584-g002">Figure 2E versus 2O</xref>; <italic>P</italic> value = 0.0064).</p><fig id="pgen-1002584-g002" position="float"><object-id pub-id-type="doi">10.1371/journal.pgen.1002584.g002</object-id><label>Figure 2</label><caption><title><italic>Mpped2</italic> and <italic>casp9</italic> knockdowns result in defective kidney development.</title><p>(A–E) Whole mount <italic>in situ</italic> hybridization in control embryos demonstrates normal expression of the global kidney marker <italic>pax2a</italic> (A: lateral view; B: dorsal view), the glomerular marker <italic>nephrin</italic> (C), and the tubular markers <italic>slc20a1a</italic> (proximal tubule, D), and <italic>slc12a3</italic> (distal tubule, E) at 48 hours post fertilization (hpf). (F–J) <italic>Mpped2</italic> morpholino (MO) knockdown embryos develop glomerular gene expression defects (F–H, arrowheads), but tubular marker expression is normal (I, J). (K–O) <italic>Casp9</italic> MO knockdown embryos demonstrate reduced glomerular gene expression (K–M, arrowheads) and shortened distal tubules (O). (P) Quantification of observed abnormalities per number of embryos reveal significant differences in expression of <italic>pax2a</italic> and <italic>nephrin</italic> in response to knockdown of both <italic>mpped2</italic> and <italic>casp9</italic> (Fisher's exact test). (Q–V) Embryos were injected with control, <italic>mpped2</italic>, <italic>or casp9</italic> MO at the one-cell stage and subsequently injected with 70,000 MW fluorescent rhodamine dextran at 80 hpf. Dextran fluorescence was monitored over the next 48 hours. All dextran-injected embryos show equal loading into the cardiac sinus venosus at 2 hours post-injection (2 hpi/82 hpf; Q, S, U). Compared to control MO-injected embryos (R) and <italic>mpped2</italic> knockdown embryos (T), knockdown of <italic>casp9</italic> resulted in reduced dextran clearance at 48 hpi as shown by increased trunk fluorescence (V). (W) <italic>Casp9</italic> knockdown results in increased susceptibility to edema formation both spontaneously (−dex) (<italic>P</italic> value = 0.0234, Fisher's exact test) and after dextran challenge (+dex) (<italic>P</italic> value<0.0001). Embryos injected with both MO and dextran did not survive to 6 dpf (N/A). (X) Edema develops earlier and with higher frequency in <italic>casp9</italic> morphants following injection of the nephrotoxin gentamicin.</p></caption><graphic xlink:href="pgen.1002584.g002"></graphic></fig><p><italic>Casp9</italic> morphants displayed diminished clearance of 70,000 MW fluorescent dextran 48 hours after injection into the sinus venosus compared to controls, revealing significant functional consequences of <italic>casp9</italic> knockdown (<xref ref-type="fig" rid="pgen-1002584-g002">Figure 2Q–2V</xref>). No clearance abnormalities were observed in <italic>mpped2</italic> morphants. The occurrence of abdominal edema is a non-specific finding that is frequently observed in zebrafish embryos with kidney defects. We examined the occurrence of edema in <italic>mpped2</italic> and <italic>casp9</italic> knockdown embryos at 4 and 6 days post fertilization (dpf), both in the absence and presence of dextran, and observed a significant increase in edema prevalence in <italic>casp9</italic> with (<italic>P</italic> value<0.0001) and without (<italic>P</italic> value = 0.0234) dextran challenge but not in <italic>mpped2</italic> morphants (<xref ref-type="fig" rid="pgen-1002584-g002">Figure 2W</xref>).</p><p>In order to further demonstrate differences in kidney function in response to knockdown of <italic>mpped2</italic> and <italic>casp9</italic>, we injected the nephrotoxin gentamicin which predictably causes edema in a subset of embryos. Casp9 morphants were more susceptible to developing edema compared to both controls and mpped2 morphants (<xref ref-type="fig" rid="pgen-1002584-g002">Figure 2X</xref>). In addition, edema developed earlier and was more severe, encompassing a greater area of the entire embryo (<xref ref-type="supplementary-material" rid="pgen.1002584.s009">Figure S9</xref>). Together, these findings suggest that <italic>casp9</italic> and <italic>mpped2</italic> knockdowns result in altered kidney gene expression and function. Specifically, abnormal expression of <italic>pax2a</italic> and <italic>nephrin</italic> in casp9 morphants in addition to dextran retention and edema formation suggest loss of <italic>casp9</italic> impacts glomerular development and function.</p><p>The lead SNP at the <italic>MPPED2</italic> locus is located approximately 100 kb upstream of the gene metallophosphoesterase domain containing 2 (<italic>MPPED2</italic>), which is highly evolutionary conserved and encodes a protein with metallophosphoesterase activity <xref rid="pgen.1002584-Tyagi1" ref-type="bibr">[18]</xref>. It has been recognized for a role in brain development and tumorigenesis <xref rid="pgen.1002584-Schwartz1" ref-type="bibr">[19]</xref> but thus far not for kidney function.</p><p>To determine whether the association at our newly identified eGFRcrea loci was primarily due to creatinine metabolism or renal function, we compared the relative associations between eGFRcrea and eGFR estimated using cystatin C (eGFRcys) (<xref ref-type="supplementary-material" rid="pgen.1002584.s010">Figure S10</xref>, <xref ref-type="supplementary-material" rid="pgen.1002584.s012">File S1</xref>). The new loci showed similar effect sizes and consistent effect directions for eGFRcrea and eGFRcys, suggesting a relation to renal function rather than to creatinine metabolism. Placing the results of these 6 loci in context with our previously identified loci <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref> (23 known and 6 novel), 18 were associated with CKD at a 0.05 significance level (odds ratio, OR, from 1.05 to 1.26; <italic>P</italic> values from 3.7×10<sup>−16</sup> to 0.01) and 11 with CKD45 (OR from 1.08 to 1.34; <italic>P</italic> values from 1.1×10<sup>−5</sup> to 0.047; <xref ref-type="supplementary-material" rid="pgen.1002584.s011">Figure S11</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s027">Table S15</xref>).</p><p>When we examined these 29 renal function loci by age group, sex, diabetes and hypertension status (<xref ref-type="supplementary-material" rid="pgen.1002584.s028">Tables S16</xref>, <xref ref-type="supplementary-material" rid="pgen.1002584.s029">S17</xref>, <xref ref-type="supplementary-material" rid="pgen.1002584.s030">S18</xref>, and <xref ref-type="supplementary-material" rid="pgen.1002584.s010">S19</xref>), we observed consistent associations with eGFRcrea for most loci across all strata, with only two exceptions: <italic>UMOD</italic> had a stronger association in older individuals (<italic>P</italic> value for difference 8.4×10<sup>−13</sup>) and in those with hypertension (<italic>P</italic> value for difference 0.002), and <italic>CDK12</italic> was stronger in younger subjects (<italic>P</italic> value for difference 0.0008). We tested the interaction between age and rs11078903 in one of our largest studies, the ARIC study. The interaction was significant (<italic>P</italic> value = 0.0047) and direction consistent with the observed between-strata difference.</p><p>Finally, we tested for associations between our 6 new loci and CKD related traits. The new loci were not associated with urinary albumin-to-creatinine ratio (UACR) or microalbuminuria <xref rid="pgen.1002584-Boger1" ref-type="bibr">[20]</xref> (<xref ref-type="supplementary-material" rid="pgen.1002584.s032">Tables S20</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s033">S21</xref>), with blood pressure from the ICBP Consortium <xref rid="pgen.1002584-The1" ref-type="bibr">[21]</xref> (<xref ref-type="supplementary-material" rid="pgen.1002584.s034">Table S22</xref>) or with myocardial infarction from the CARDIoGRAM Consortium <xref rid="pgen.1002584-Schunkert1" ref-type="bibr">[22]</xref> (<xref ref-type="supplementary-material" rid="pgen.1002584.s035">Table S23</xref>).</p></sec><sec id="s3"><title>Discussion</title><p>We have extended prior knowledge of common genetic variants for kidney function <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>–<xref rid="pgen.1002584-Gudbjartsson1" ref-type="bibr">[11]</xref>, <xref rid="pgen.1002584-Pattaro1" ref-type="bibr">[23]</xref> by performing genome-wide association tests within strata of key CKD risk factors, including age, sex, diabetes, and hypertension, thus uncovering 6 loci not previously known to be associated with renal function in population-based studies (<italic>MPPED2</italic>, <italic>DDX1</italic>, <italic>CASP9</italic>, <italic>SLC47A1</italic>, <italic>CDK12</italic>, <italic>INO80</italic>). In contrast to our prior genome-wide analysis <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref>, the majority of the new loci uncovered in the present analysis have little known prior associations with renal function. This highlights a continued benefit of the GWAS approach by using large sample sizes to infer new biology.</p><p>Despite our hypothesis that genetic effects are modified by CKD risk factors, most of the identified variants did not exhibit strong cross-strata differences. This highlights that many genetic associations with kidney function may be shared across risk factor strata. The association of several of these loci with kidney function in African Americans underscores the generalizability of identified renal loci across ethnicities. Zebrafish knockdown of <italic>mpped2</italic> resulted in abnormal podocyte anatomy as assessed by expression of glomerular markers, and loss of <italic>casp9</italic> led to altered podocyte and distal tubular marker expression, decreased dextran clearance, edema, and enhanced susceptibility to gentamicin-induced kidney damage. These findings demonstrate the potential importance of these genes with respect to renal function and illustrate that zebrafish are a useful <italic>in vivo</italic> model to explore the functional consequences of GWAS-identified genes.</p><p>Despite these strengths, there are some limitations of our study that warrant discussion. Although we used cystatin C to separate creatinine metabolism from true filtration loci, SNPs within the cystatin C gene cluster have been shown to be associated with cystatin C levels <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, which might result in some degree of misclassification in absolute levels. While we used standard definitions of diabetes and hypertension in the setting of population-based studies, these may differ from those definitions used in clinical practice. In addition, we were unable to differentiate the use of anti-hypertension medications from other clinical indications of these agents or type 1 from type 2 diabetes. The absence of association between our six newly discovered SNPs and the urinary albumin to creatinine ratio, blood pressure, and cardiovascular disease may have resulted from disparate genetic underpinnings of these traits, the overall small effect sizes, or the cross-sectional nature of our explorations; and we were unable to differentiate between these potential issues. Finally, power was modest to detect between-strata heterogeneity.</p><p>With increased sample size and stratified analyses, we have identified additional loci for kidney function that continue to have novel biological implications. Our primary findings suggest that there is substantial generalizability of SNPs associations across strata of important CKD risk factors, specifically with hypertension and diabetes.</p></sec><sec sec-type="materials|methods" id="s4"><title>Materials and Methods</title><sec id="s4a"><title>Phenotype definition</title><p>Serum creatinine and cystatin C were measured as detailed in <xref ref-type="supplementary-material" rid="pgen.1002584.s013">Tables S1</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s014">S2</xref>. To account for between-laboratory variation, serum creatinine was calibrated to the US nationally representative National Health and Nutrition Examination Study (NHANES) standards in all discovery and replication studies as described previously <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Fox1" ref-type="bibr">[24]</xref>, <xref rid="pgen.1002584-Coresh2" ref-type="bibr">[25]</xref>. GFR based on serum creatinine (eGFRcrea) was estimated using the four-variable MDRD Study equation <xref rid="pgen.1002584-Levey2" ref-type="bibr">[26]</xref>. GFR based on cystatin C (eGFRcys) was estimated as eGFRcys = 76.7×(serum cystatin C)<sup>−1.19</sup><xref rid="pgen.1002584-Stevens1" ref-type="bibr">[27]</xref>. eGFRcrea and eGFRcys values<15 ml/min/1.73 m<sup>2</sup> were set to 15, and those >200 were set to 200 ml/min/1.73 m<sup>2</sup>. CKD was defined as eGFRcrea <60 ml/min/1.73 m<sup>2</sup> according to the National Kidney Foundation guidelines <xref rid="pgen.1002584-National1" ref-type="bibr">[28]</xref>. A more severe CKD phenotype, CKD45, was defined as eGFRcrea <45 ml/min/1.73 m<sup>2</sup>. Control individuals for both CKD and CKD45 analyses were defined as those with eGFRcrea >60 ml/min/1.73 m<sup>2</sup>.</p></sec><sec id="s4b"><title>Covariate definitions</title><p>In discovery and replication cohorts, diabetes was defined as fasting glucose ≥126 mg/dl, pharmacologic treatment for diabetes, or by self-report. Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or pharmacologic treatment for hypertension.</p></sec><sec id="s4c"><title>Discovery analyses</title><p>Genotyping was conducted as specified in <xref ref-type="supplementary-material" rid="pgen.1002584.s016">Table S4</xref>. After applying quality-control filters to exclude low-quality SNPs or samples, each study imputed up to ∼2.5 million HapMap-II SNPs, based on the CEU reference samples. Imputed genotypes were coded as the estimated number of copies of a specified allele (allelic dosage). Additional, study-specific details can be found in <xref ref-type="supplementary-material" rid="pgen.1002584.s013">Table S1</xref>.</p></sec><sec id="s4d"><title>Primary association analysis</title><p>A schematic view of our complete analysis workflow is presented in <xref ref-type="supplementary-material" rid="pgen.1002584.s001">Figure S1</xref>. Using data from 26 population-based studies of individuals of European ancestry, we performed GWA analyses of the following phenotypes: 1) log<sub>e</sub>(eGFRcrea), log<sub>e</sub>(eGFRcys), CKD, and CKD45 overall and 2) log<sub>e</sub>(eGFRcrea) and CKD stratified by diabetes status, hypertension status, age group (≤/>65 years), and sex. GWAS of log<sub>e</sub>(eGFRcrea) and log<sub>e</sub>(eGFRcys) were based on linear regression. GWAS of CKD and CKD45 were performed in studies with at least 25 cases (i.e. all 26 studies for CKD and 11 studies for CKD45) and were based on logistic regression. Additive genetic effects were assumed and models were adjusted for age and, where applicable, for sex, study site and principal components. Imputation uncertainty was accounted for by including allelic dosages in the model. Where necessary, relatedness was modeled with appropriate methods (see <xref ref-type="supplementary-material" rid="pgen.1002584.s013">Table S1</xref> for study-specific details). Before including in the meta-analysis, all GWA data files underwent to a careful quality control, performed using the GWAtoolbox package in R (<ext-link ext-link-type="uri" xlink:href="http://www.eurac.edu/GWAtoolbox.html">www.eurac.edu/GWAtoolbox.html</ext-link>) <xref rid="pgen.1002584-Fuchsberger1" ref-type="bibr">[29]</xref>.</p><p>Meta-analyses of study-specific SNP-association results, assuming fixed effects and using inverse-variance weighting, i.e.: the pooled effect <inline-formula><inline-graphic xlink:href="pgen.1002584.e001.jpg" mimetype="image"></inline-graphic></inline-formula> is estimated as <inline-formula><inline-graphic xlink:href="pgen.1002584.e002.jpg" mimetype="image"></inline-graphic></inline-formula>, where <inline-formula><inline-graphic xlink:href="pgen.1002584.e003.jpg" mimetype="image"></inline-graphic></inline-formula> is the effect of the SNP on the outcome in the <italic>i</italic><sup>th</sup> study, <italic>K</italic> is the number of studies, and <inline-formula><inline-graphic xlink:href="pgen.1002584.e004.jpg" mimetype="image"></inline-graphic></inline-formula> is the weight given to the <italic>i</italic><sup>th</sup> study. The meta-analyses were performed using METAL <xref rid="pgen.1002584-Willer1" ref-type="bibr">[30]</xref>, with genomic control correction applied across all imputed SNPs <xref rid="pgen.1002584-Devlin1" ref-type="bibr">[31]</xref> if the inflation factor λ>1 at both the individual study level and after the meta-analysis. SNPs with minor allele frequency (MAF)<1% were excluded. All SNPs with a meta-analysis <italic>P</italic> value≤5×10<sup>−8</sup> for any trait or any stratum were deemed genome-wide significant <xref rid="pgen.1002584-Peer1" ref-type="bibr">[32]</xref>.</p><p>In the eGFRcrea analyses, after excluding loci that were previously reported <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref>, we selected for replication all SNPs with <italic>P</italic> value<5×10<sup>−8</sup> in any trait or stratum that were independent (defined by pairwise <italic>r</italic><sup>2</sup><0.2), in the primary association analysis. This yielded five SNPs in five independent loci. The same criterion was applied to the CKD analysis, where no SNPs passed the selection threshold. Given the smaller number of cases with severe CKD resulting in less statistical power, a different selection strategy was adopted for the CKD45 analysis: selected for replication were SNPs with discovery <italic>P</italic> value≤5×10<sup>−6</sup>, MAF≥5%, and homogeneous effect size across studies (I<sup>2</sup>≤25%). Four additional SNPs were thereby selected for replication from the CKD45 analysis.</p></sec><sec id="s4e"><title>Direction test to identify SNPs for replication</title><p>In addition to identifying SNPs for replication based on the genome-wide significance threshold from a fixed effect model meta-analysis, we performed a “direction test” to identify additional SNPs for which between-study heterogeneity in effect size might have obscured the overall association that was nevertheless highly consistent in the direction of allelic effects. Under the null hypothesis of no association, the <italic>a priori</italic> probability that a given effect allele of a SNP has either a positive or negative association with eGFRcrea is 0.5. Because the meta-analysis includes independent studies, the number of concordant effect directions follows a binomial distribution. Therefore, we tested whether the number of discovery cohorts with the same sign of association (i.e. direction of effect) was greater than expected by chance given the binomial distribution and a null expectation of equal numbers of associations with positive and negative sign. The test was only applied for eGFRcrea in the overall analysis. Multiple testing was controlled by applying the same <italic>P</italic> value threshold of 5×10<sup>−8</sup> as in the overall GWAS. Given that no SNP met this criterion, we selected for replication one novel SNP with the lowest <italic>P</italic> value of 4.0×10<sup>−7</sup>.</p></sec><sec id="s4f"><title>Genome-wide between-strata difference test to identify SNPs for replication</title><p>Based on the results of the stratified GWAS of eGFRcrea and CKD, for each SNP we tested the hypothesis whether the effect of a SNP on eGFRcrea or CKD was the same between strata (null hypothesis), i.e. diabetes versus non-diabetes subjects, hypertensive versus normotensive, younger versus older, females versus males. We used a two-sample test defined as Z = (b<sub>1</sub>−b<sub>2</sub>)/(SE(b<sub>1</sub>)<sup>2</sup>+SE(b<sub>2</sub>)<sup>2</sup>)<sup>0.5</sup>, with b<sub>1</sub> and b<sub>2</sub> indicating the effect estimates in the two strata and SE(b<sub>1</sub>) and SE(b<sub>2</sub>) their standard errors <xref rid="pgen.1002584-Cohen1" ref-type="bibr">[33]</xref>. For large samples, the test statistic follows a standard normal distribution. SNPs were selected for replication if they had a between-stratum difference <italic>P</italic> value≤5×10<sup>−5</sup>, an association <italic>P</italic> value≤5×10<sup>−5</sup> in one of the two strata, and MAF≥10%. Independent loci were defined using the same criteria as described above. Eleven further SNPs, one per locus, were selected for replication from the between-strata difference test.</p></sec><sec id="s4g"><title>Replication analysis</title><p>Replication was performed for a total of 21 SNPs including 5 from the overall and stratified eGFRcrea analyses, 1 from the direction test on eGFRcrea, 4 from the overall CKD45 analysis, and 11 from the between-strata difference test. Replication studies used the same phenotype definition, and had available genotypes from imputed <italic>in silico</italic> genome-wide SNP data or <italic>de novo</italic> genotyping. The same association analyses including the identical stratifications were performed as in discovery studies. Details can be found in the <xref ref-type="supplementary-material" rid="pgen.1002584.s014">Tables S2</xref>, <xref ref-type="supplementary-material" rid="pgen.1002584.s017">S5</xref> and <xref ref-type="supplementary-material" rid="pgen.1002584.s018">S6</xref>. Study-specific replication results for the selected SNPs were combined using the same meta-analysis approach and software as in the discovery stage. One-sided <italic>P</italic> values were derived with regard to the effect direction found in the discovery stage. Based on the <italic>P</italic> value distribution of all SNPs submitted for replication (the 10 from eGFRcrea and CKD45 and the 11 from the between strata difference test), we estimated the False Discovery Rate as a q-value using the QVALUE <xref rid="pgen.1002584-Storey1" ref-type="bibr">[34]</xref> package in R. SNPs with q-value<0.05 were called significantly replicating, thus specifying a list of associations expected to include not more than 5% false positives.</p><p>Finally, study-specific results from both the discovery and replication stage were combined in a joint inverse-variance weighted fixed-effect meta-analysis and the two-sided <italic>P</italic> values were compared to the genome-wide significance threshold of 5×10<sup>−8</sup> to test whether a SNP was genome-wide significant. Between-study heterogeneity of replicated SNPs was quantified by the I<sup>2</sup> statistic <xref rid="pgen.1002584-Higgins1" ref-type="bibr">[35]</xref>.</p></sec><sec id="s4h"><title>Replication genotyping</title><p>For <italic>de novo</italic> genotyping in 10,446 samples from KORA F3, KORA F4, SAPHIR and SAPALDIA, the MassARRAY system at the Helmholtz Zentrum (München, Germany) was used, using Assay Design v3.1.2 and the iPLEX chemistry (Sequenom, San Diego, USA). Assay design failed for rs1322199 and genotyping was not performed. Ten percent of the spectra were checked by two independent, trained persons, and 100% concordance between investigators was obtained. SNPs with a <italic>P</italic> value<0.001 when testing for Hardy-Weinberg equilibrium (rs10490130, rs10068737, rs11078903), SNPs with call rate <90% (rs500456 in KORA F4 only) or monomorphic SNPs (rs2928148) were excluded from analyses without attempting further genotyping. The call rates of rs4149333 and rs752805 were near 0% on the MassARRAY system. These SNPs were thus genotyped on a 7900HT Fast Real-Time PCR System (Applied Biosystems, Foster City, USA). Mean call rate across all studies and SNPs ranged from 96.8% (KORA F4) to 99% (SAPHIR). Duplicate genotyping was performed in at least 14% of the subjects in each study with a concordance of 95–100% (median 100%). In the Ogliastra Genetic Park Replication Study (n = 3000) <italic>de novo</italic> genotyping was conducted on a 7900HT Fast Real-Time PCR System (Applied Biosystems, Foster City, USA), with a mean call rate of 99.4% and 100% concordance of SNPs genotyped in duplicate.</p></sec><sec id="s4i"><title>Between-strata analyses for candidate SNPs in replication samples</title><p>Twenty-nine SNPs, including the 6 novel loci reported in the current manuscript along with 23 previously confirmed to be associated with renal function <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref>, were tested for differential effects between the strata. The same Z statistics as described for discovery (above) was used and the Bonferroni-adjusted significance level was set to 0.10/29 = 0.003.</p><p>SNP-by-age interaction, for the one SNP showing significantly different effects between strata of age, was tested in the ARIC study by fitting a linear model on log(eGFRcrea) adjusted for sex, recruitment site, the first and the seventh genetic principal components (only these two were associated with the outcome at <italic>P</italic> value<0.05). Both the interaction term and the terms for the main effects of age and the SNP were included in the model.</p></sec><sec id="s4j"><title>Power to assess between-strata effect difference</title><p>To assess genome-wide between-strata differences, with alpha = 5×10<sup>−8</sup> and power = 80%, the maximum detectable difference was 0.025 when comparing nonDM versus DM and 0.015 when comparing nonHTN versus HTN. Similarly, when testing for between-strata differences the 29 known and new loci (Bonferroni-corrected alpha = 0.003) in the combined sample (n = ∼125,000 in nonDM and n = ∼13,000 in DM) we had 80% power to detect differences as large as 0.035.</p></sec><sec id="s4k"><title>Look-up in African Americans (CARe)</title><p>For each of the 6 lead SNPs identified in our European ancestry samples, we extracted eGFR association statistics from a genome-wide study in the CARe African ancestry consortium <xref rid="pgen.1002584-Liu1" ref-type="bibr">[12]</xref>. We further investigated potential allelic heterogeneity across ethnicities by examining the 250 kb flanking region surrounding each lead SNP to determine whether other SNPs with stronger associations exist in each region. A SNP with the smallest association <italic>P</italic> value with MAF>0.03 was considered the top SNP in the African ancestry sample. We defined statistical significance of the identified lead SNP in African ancestry individuals based on a region-specific Bonferroni correction. The number of independent SNPs was determined based on the variance inflation factor (VIF) with a recursive calculation within a sliding window of 50 SNPs and pairwise r<sup>2</sup> of 0.2. These analyses were performed using PLINK.</p></sec><sec id="s4l"><title>Analyses of related phenotypes</title><p>For each replicating SNP, we obtained association results for urinary albumin-to-creatinine ratio and microalbuminuria from our previous genome-wide association analysis <xref rid="pgen.1002584-Boger1" ref-type="bibr">[20]</xref>, and for blood pressure and myocardial infarction from genome-wide association analysis from the ICBP <xref rid="pgen.1002584-The1" ref-type="bibr">[21]</xref> and CARDIoGRAM <xref rid="pgen.1002584-Schunkert1" ref-type="bibr">[22]</xref> consortia, respectively.</p></sec><sec id="s4m"><title>eSNP analysis</title><p>Significant renal SNPs were searched against a database of expression SNPs (eSNP) including the following tissues: fresh lymphocytes <xref rid="pgen.1002584-Goring1" ref-type="bibr">[36]</xref>, fresh leukocytes <xref rid="pgen.1002584-Idaghdour1" ref-type="bibr">[37]</xref>, leukocyte samples in individuals with Celiac disease <xref rid="pgen.1002584-Heap1" ref-type="bibr">[38]</xref>, lymphoblastoid cell lines (LCL) derived from asthmatic children <xref rid="pgen.1002584-Dixon1" ref-type="bibr">[39]</xref>, HapMap LCL from 3 populations <xref rid="pgen.1002584-Stranger1" ref-type="bibr">[40]</xref>, a separate study on HapMap CEU LCL <xref rid="pgen.1002584-Kwan1" ref-type="bibr">[41]</xref>, peripheral blood monocytes <xref rid="pgen.1002584-Heinzen1" ref-type="bibr">[42]</xref>, <xref rid="pgen.1002584-Zeller1" ref-type="bibr">[43]</xref>, adipose <xref rid="pgen.1002584-Emilsson1" ref-type="bibr">[44]</xref>, <xref rid="pgen.1002584-Greenawalt1" ref-type="bibr">[45]</xref> and blood samples <xref rid="pgen.1002584-Emilsson1" ref-type="bibr">[44]</xref>, 2 studies on brain cortex <xref rid="pgen.1002584-Heinzen1" ref-type="bibr">[42]</xref>, <xref rid="pgen.1002584-Webster1" ref-type="bibr">[46]</xref>, 3 large studies of brain regions including prefrontal cortex, visual cortex and cerebellum (Emilsson, personal communication), liver <xref rid="pgen.1002584-Greenawalt1" ref-type="bibr">[45]</xref>, <xref rid="pgen.1002584-Schadt1" ref-type="bibr">[47]</xref>, osteoblasts <xref rid="pgen.1002584-Grundberg1" ref-type="bibr">[48]</xref>, skin <xref rid="pgen.1002584-Ding1" ref-type="bibr">[49]</xref> and additional fibroblast, T cell and LCL samples <xref rid="pgen.1002584-Dimas1" ref-type="bibr">[50]</xref>. The collected eSNP results met criteria for statistical significance for association with gene transcript levels as described in the original papers.</p><p>A second expression analysis of 81 biopsies from normal kidney cortex samples was performed as described previously <xref rid="pgen.1002584-Rodwell1" ref-type="bibr">[51]</xref>, <xref rid="pgen.1002584-Wheeler1" ref-type="bibr">[52]</xref>. Genotyping was performed using Affymetrix 6.0 Genome-wide chip and called with GTC Software (Affymetrix). For eQTL analyses, expression probes (Affymetrix U133set) were linked to SNP probes with >90% call-rate using RefSeq annotation (Affymetrix build a30). <italic>P</italic> values for eQTLs were calculated using linear multivariable regression in both cohorts and then combined using Fisher's combined probability test (see also <xref rid="pgen.1002584-Wheeler1" ref-type="bibr">[52]</xref>). Pairwise LD was calculated using SNAP <xref rid="pgen.1002584-Johnson1" ref-type="bibr">[53]</xref> on the CEU HapMap release 22.</p></sec><sec id="s4n"><title>Zebrafish functional experiments</title><p>Zebrafish were maintained according to established IACUC protocols. Briefly, we injected zebrafish embryos with newly designed (mpped2, ddx1) or previously validated (casp9 <xref rid="pgen.1002584-Sidi1" ref-type="bibr">[54]</xref>) morpholino antisense oligonucleotides (MO, GeneTools, Philomath OR) at the one-cell stage at various doses. We fixed embryos in 4% PFA at the appropriate stages for in situ hybridization (<ext-link ext-link-type="uri" xlink:href="http://zfin.org/ZFIN/Methods/ThisseProtocol.html">http://zfin.org/ZFIN/Methods/ThisseProtocol.html</ext-link>). Different anatomic regions of the kidney were visualized using a panel of 4 established markers: <italic>pax2a</italic> (global kidney marker) <xref rid="pgen.1002584-Drummond1" ref-type="bibr">[15]</xref>, <italic>nephrin</italic> (podocyte marker) <xref rid="pgen.1002584-KramerZucker1" ref-type="bibr">[16]</xref>, <italic>slc20a1a</italic> (proximal tubule) <xref rid="pgen.1002584-Wingert1" ref-type="bibr">[17]</xref>, and <italic>slc12a3</italic> (distal tubule marker) <xref rid="pgen.1002584-Wingert1" ref-type="bibr">[17]</xref>. Abnormalities in gene expression were independently scored by two investigators. We compared the number of abnormal morphant embryos to control embryos, injected with a standard control MO designed by GeneTools, with the Fisher's exact test, at the Bonferroni-corrected significance level of 0.0125, i.e.: 0.05/4 markers. We documented the development of gross edema at 4 and 6 days post-fertilization in live embryos.</p><p>We performed dextran clearance experiments following previously described protocols <xref rid="pgen.1002584-Hentschel1" ref-type="bibr">[55]</xref>. Briefly, 80 hours after MO injection, we anesthetized embryos in 4 mg/ml Tricaine in embryo water (1∶20 dilution), then positioned embryos on their back in a 1% agarose injection mold. We injected an equal volume of tetramethylrhodamine dextran (70,000 MW; Invitrogen) into the cardiac sinus venosus of each embryo. We then returned the embryos to fresh embryo water. Using fluorescence microscopy, we imaged the embryos at 2 hours post-injection (82 hpf) to demonstrate equal loading, then at 48 hours post-injection (128 hpf) to evaluate dextran clearance.</p><p>Embryos were injected with control, mpped2, or casp9 MOs at the one-cell stage. At 48 hpf, embryos were manually dechorionated, anesthetized in a 1∶20 dilution of 4 mg/ml Tricaine in embryo water, and oriented on a 1% agarose injection mold. As previously described <xref rid="pgen.1002584-Hentschel2" ref-type="bibr">[56]</xref>, embryos were injected with equal volumes of 10 mg/ml gentamicin (Sigma) in the cardiac sinus venosus, returned to fresh embryo water, and subsequently scored for edema (prevalence, time of onset) over the next 3 days.</p></sec></sec><sec sec-type="supplementary-material" id="s5"><title>Supporting Information</title><supplementary-material content-type="local-data" id="pgen.1002584.s001"><label>Figure S1</label><caption><p>Flowchart of the project.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s001.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s002"><label>Figure S2</label><caption><p>Genome-wide −log<sub>10</sub><italic>P</italic> values plot from stage 1 discovery meta-analysis. Plots show the discovery analysis of eGFRcrea in the overall group, with known loci <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref> highlighted in orange and novel loci highlighted in blue (A), and in strata of the main CKD risk factors (B, C, D, and E), with complementary groups being contrasted each other. The dotted line indicates the genome-wide significance threshold at <italic>P</italic> value = 5×10<sup>−8</sup>. The unmarked locus is <italic>RNASEH</italic>2C on chromosome 11, colored in gray despite genome-wide significance. The P value for the current stage 1 discovery for rs4014195 was 2.7×10<sup>−9</sup>. This locus previously did not replicate <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref>; when we additionally considered our prior non-overlapping in silico and de novo replication data, the current stage 2 <italic>P</italic> value was 0.8832, yielding a combined stage 1+stage 2 <italic>P</italic> value of 2.6×10<sup>−7</sup>. Therefore, we did not submit this SNP for further replication.</p><p>(PDF)</p></caption><media xlink:href="pgen.1002584.s002.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s003"><label>Figure S3</label><caption><p>Quantile-quantile plots of observed versus expected −log<sub>10</sub><italic>P</italic> values from the discovery analysis of eGFRcrea overall (A) and by strata of the main CKD risk factors (B). The orange line and its 95% confidence interval (shaded area) represent the null hypothesis of no association. In panel (A), results are compared when considering all SNPs (black dots) and when removing SNPs from loci that were already reported in previous GWAS <xref rid="pgen.1002584-Kottgen1" ref-type="bibr">[8]</xref>, <xref rid="pgen.1002584-Kottgen2" ref-type="bibr">[9]</xref> (orange dots). The meta-analysis inflation factor λ is reported along with the discovery sample size. Individual-study minimum, maximum and median λs are also reported for comparison. Genomic-control correction was applied twice: on individual study results, before the meta-analysis, and on the meta-analysis results.</p><p>(PDF)</p></caption><media xlink:href="pgen.1002584.s003.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s004"><label>Figure S4</label><caption><p>Regional association plots for the six new loci in the European ancestry discovery samples: (A) <italic>MPPED2</italic>; (B) <italic>DDX1</italic>; (C) <italic>SLC47A1</italic>; (D) <italic>CASP9</italic>; (E) <italic>CDK12</italic>; (F) <italic>INO80</italic>. −log<sub>10</sub><italic>P</italic> values are plotted versus genomic position(build 36). The lead SNP in each region is labeled. Other SNPs in each region are color-coded based on their LD to the lead SNP(LD based on the HapMap CEU, see color legend). Gene annotations are based on UCSC Genome Browser(RefSeq Genes, build 36) and arrows indicate direction of transcription. Graphs were generated using the stand-alone version of LocusZoom <xref rid="pgen.1002584-Pruim1" ref-type="bibr">[57]</xref>, version 1.1.</p><p>(PDF)</p></caption><media xlink:href="pgen.1002584.s004.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s005"><label>Figure S5</label><caption><p>Forest plots of the six novel loci in the discovery phase.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s005.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s006"><label>Figure S6</label><caption><p>Results from discovery meta-analysis of eGFRcrea for the six new loci: overall sample and all strata are considered. Reported is the effect size on log(eGFRcrea) and its 95% confidence interval. The stratum where the SNP was discovered is marked with a triangle for discovery based on meta-analysis <italic>P</italic> value or with a circle for discovery based on direction test.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s006.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s007"><label>Figure S7</label><caption><p>Regional association plots for the six new loci in the African ancestry CARe samples: (A) <italic>MPPED2</italic>; (B) <italic>DDX1</italic>; (C) <italic>SLC47A1</italic>; (D) <italic>CASP9</italic>; (E) <italic>CDK12</italic>; (F) <italic>INO80.</italic> −log<sub>10</sub><italic>P</italic> values are plotted versus genomic position (build 36). The lead SNP in each region is labeled and identified by a blue arrow and blue <italic>P</italic> value. The SNP with the smallest <italic>P</italic> value in the region is indicated by a red arrow. Other SNPs in each region are color-coded based on their LD to the lead SNP (based on the HapMap YRI, see color legend). Gene annotation is based on UCSC Genome Browser (RefSeq Genes, build 36) and arrows indicate direction of transcription. Graphs were generated using the stand-alone version of LocusZoom <xref rid="pgen.1002584-Pruim1" ref-type="bibr">[57]</xref>, version 1.1.</p><p>(PDF)</p></caption><media xlink:href="pgen.1002584.s007.pdf"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s008"><label>Figure S8</label><caption><p>Ddx1 knockdown does not affect kidney gene expression. (A–E) Uninjected control embryos show normal kidney development as demonstrated by in situ hybridization for the renal markers <italic>pax2a</italic> (A, B), <italic>nephrin</italic> (C), <italic>slc20a1a</italic> (D) and <italic>slc12a3</italic> (E). (F–J) <italic>Ddx1</italic> morpholino(MO)-injected embryos do not show significant changes in renal marker expression. (K) Number of observed abnormalities per number of embryos examined at 400 uM MO injection for renal gene expression analysis.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s008.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s009"><label>Figure S9</label><caption><p>Casp9 and mpped2 knockdown embryos are more susceptible to gentamicin-induced kidney injury. Compared to control embryos (A), casp9 and mpped2 knockdown embryos develop edema at 103 hpf (C, E), suggestive of a renal defect. When injected with gentamicin, a nephrotoxin that reproducibly induces edema in control embryos (B), mpped2 and casp9 knockdown embryos develop edema earlier, more frequently, and in a more severe fashion (D, F). Whereas control embryos primarily develop cardiac edema, mpped2 and casp9 knockdown embryos display cardiac (arrowhead), ocular (black arrow), and visceral (white arrow) edema, demonstrating that mpped2 and casp9 knockdown predisposes embryos to kidney injury. (G) Quantification of edema prevalence in control, mpped2, and casp9 knockdown embryos 2, 22, and 55 hours post-injection (hpi) of gentamicin. These numbers are presented graphically in <xref ref-type="fig" rid="pgen-1002584-g002">Figure 2X</xref>.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s009.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s010"><label>Figure S10</label><caption><p>Comparison of the effect size on eGFRcrea and on eGFRcys for the lead SNPs of known and new loci. Results are based on the largest sample size available for each locus, i.e. the combined discovery and replication sample for the novel loci (N = 130,600), the discovery sample only for the known loci (N = 74,354). Sign of effect estimates has been changed to reflect the effects of the eGFRcrea lowering alleles. Original beta coefficients and their standard errors for the two traits can be downloaded from the File S1.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s010.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s011"><label>Figure S11</label><caption><p>Odds ratios (ORs) and 95% confidence intervals of CKD and CKD45 for the lead SNPs of all known and new loci, sorted by decreasing OR of CKD.</p><p>(TIF)</p></caption><media xlink:href="pgen.1002584.s011.tif"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s012"><label>File S1</label><caption><p>Effect size on eGFRcrea and on eGFRcys for the lead SNPs of known and new loci.</p><p>(XLSX)</p></caption><media xlink:href="pgen.1002584.s012.xlsx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s013"><label>Table S1</label><caption><p>Study-specific methods and full acknowledgments—discovery studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s013.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s014"><label>Table S2</label><caption><p>Study-specific methods and full acknowledgments—replication studies and functional follow-up studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s014.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s015"><label>Table S3</label><caption><p>Characteristics of stage 1 discovery studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s015.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s016"><label>Table S4</label><caption><p>Study-specific genotyping information for stage 1 discovery studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s016.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s017"><label>Table S5</label><caption><p>Characteristics of stage 2 replication studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s017.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s018"><label>Table S6</label><caption><p>Study-specific genotyping information for stage 2 <italic>in silico</italic> replication studies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s018.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s019"><label>Table S7</label><caption><p>Top four SNPs from the CKD45 analysis.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s019.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s020"><label>Table S8</label><caption><p>Loci identified by the test for differential effects between strata in the GWAS. Results are sorted by trait, group and chromosome. For each SNP, the <italic>P</italic> value of the test for difference between strata is reported.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s020.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s021"><label>Table S9</label><caption><p>Imputation quality of replicated SNPs in all discovery and replication studies: median MACH-Rsq and interquartile range (IQR) are reported.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s021.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s022"><label>Table S10</label><caption><p>Effects of novel and known loci on log(eGFRcrea) in the overall population.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s022.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s023"><label>Table S11</label><caption><p>Genes nearest to loci associated with renal traits.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s023.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s024"><label>Table S12</label><caption><p>Imputation Quality (MACH-Rsq) for the best SNPs in the African ancestry samples of the CARe consortium (1.00 refers to genotyped data).</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s024.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s025"><label>Table S13</label><caption><p>Baseline characteristics of the kidney biopsies for the eQTL analysis.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s025.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s026"><label>Table S14</label><caption><p>Analysis of the new loci for eQTL status in meta-analysis of two cohorts of kidney biopsies.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s026.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s027"><label>Table S15</label><caption><p>Association of novel and known loci with CKD and CKD45: Odds Ratios (OR), 95% confidence intervals (95%CI) and <italic>P</italic> values.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s027.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s028"><label>Table S16</label><caption><p>Association between novel and known loci and log(eGFRcrea) in individuals without and with diabetes and test for difference between strata.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s028.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s029"><label>Table S17</label><caption><p>Association between novel and known loci and log(eGFRcrea) in individuals without and with hypertension and test for difference between strata.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s029.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s030"><label>Table S18</label><caption><p>Association between novel and known loci and log(eGFRcrea) in individuals younger and older than 65 years and test for difference between strata.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s030.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s031"><label>Table S19</label><caption><p>Association between novel and known loci and log(eGFRcrea) in females and in males and test for difference between strata.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s031.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s032"><label>Table S20</label><caption><p>Effects of novel loci on the logarithm of urinary albumin-to-creatinine ratio (log(UACR)) in the overall sample and by diabetes and hypertension status.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s032.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s033"><label>Table S21</label><caption><p>Effects (log odds ratios) of novel loci on microalbuminuria (MA) in the overall sample and by diabetes and hypertension status.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s033.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s034"><label>Table S22</label><caption><p>Association of novel loci with diastolic and systolic blood pressure in the ICBP consortium.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s034.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data" id="pgen.1002584.s035"><label>Table S23</label><caption><p>Association of novel loci with myocardial infarction in the CARDIoGRAM consortium.</p><p>(DOC)</p></caption><media xlink:href="pgen.1002584.s035.doc"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></sec></body><back><fn-group><fn fn-type="COI-statement"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="financial-disclosure"><p>The AGES study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Amish study was supported by grants and contracts from the NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06 (HAPI Study), U01 HL084756 and NIH K12RR023250 (University of Maryland MCRDP), the University of Maryland General Clinical Research Center, grant M01 RR 16500, the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center, and the Paul Beeson Physician Faculty Scholars in Aging Program. The ASPS research reported in this article was funded by the Austrian Science Fund (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supported the databank of the ASPS. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A Köttgen and C Hundertmark were supported by the grant KO3598/2-1 (Emmy Noether Programme) of the German Research Foundation. The BLSA was supported in part by the Intramural Research Program of the NIH (National Institute on Aging). The CHS research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at <ext-link ext-link-type="uri" xlink:href="http://www.chs-nhlbi.org/pi.htm">http://www.chs-nhlbi.org/pi.htm</ext-link>. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The ERF study was supported by grants from the Netherlands Organization for Scientific Research (NWO; Pioneergrant), Erasmus Medical Center, the Centre for Medical Systems Biology (CMSB), and the Netherlands Kidney Foundation. The Family Heart Study (FHS) work was supported in part by NIH grants 5R01HL08770003, 5R01HL08821502 (M Province) from the NHLBI and 5R01DK07568102, 5R01DK06833603 from the NIDDK (I Borecki). The Framingham Heart Study research reported in this paper was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The GENOA research was partially supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health R01 HL-87660. The Health Aging and Body Composition Study (Health ABC) was funded by the National Institutes of Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. For the KORA F3 and F4 studies, the genetic epidemiological work was funded by the NIH subcontract from the Children's Hospital, Boston, US, (HE Wichmann, IM Heid, prime grant 1 R01 DK075787-01A1), the German National Genome Research Net NGFN2 and NGFNplus (H.E.Wichmann 01GS0823; WK project A3, number 01GS0834), the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ, and by the Else Kröner-Fresenius-Stiftung (P48/08//A11/08; CA Böger, BK Krämer). The kidney parameter measurements in F3 were funded by the Else Kröner-Fresenius-Stiftung (CA Böger, BK Krämer) and the Regensburg University Medical Center, Germany; in F4 by the University of Ulm, Germany (W Koenig). Genome-wide genotyping costs in F3 and F4 was in part funded by the Else Kröner-Fresenius-Stiftung (CA Böger, BK Krämer). De novo genotyping in F3 and F4 was funded by the Else Kröner-Fresenius-Stiftung (CA Böger, BK Krämer). The KORA research platform and the MONICA Augsburg studies were initiated and financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, by the German Federal Ministry of Education and Research, and by the State of Bavaria. Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum München. The LINUX platform for computation was funded by the University of Regensburg for the Department of Epidemiology and Preventive Medicine at the Regensburg University Medical Center. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental and Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract “High-throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). We thank the staff and participants of the NHS and HPFS for their dedication and commitment. The Korcula study was supported through the grants from the Medical Research Council UK to H Campbell, AF Wright, and I Rudan and by Ministry of Science, Education, and Sport of the Republic of Croatia to I Rudan (number 108-1080315-0302). The MICROS study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). The Northern Swedish Population Health Study was supported by grants from the Swedish Natural Sciences Research Council, the European Union through the EUROSPAN project (contract no. LSHG-CT-2006-018947), the Foundation for Strategic Research (SSF), and the Linneaus Centre for Bioinformatics (LCB). The NHS renal function and albuminuria work was supported by DK66574. Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. The popgen study was supported by the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN) and the Ministry of Science, Commerce, and Transportation of the State of Schleswig-Holstein. The project has also received infrastructure support through the DFG excellence cluster “Inflammation at Interfaces.” The Sorbs study was funded by grants from the German Research Council KFO-152 (to M Stumvoll) and the IFB (Integrated Research and Treatment Center) AdiposityDiseases (K7-37 to M Stumvoll and A Tönjes). We also thank Dr. Knut Krohn (Microarray Core Facility of the Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany) for providing the genotyping platform. The research of Inga Prokopenko is funded in part through the European Community's
Seventh Framework Programme (FP7/2007–2013), ENGAGE project, grant agreement HEALTH-F4-2007- 201413. R Mägi acknowledges financial support from the European Commission under a Marie Curie Intra-European Fellowship. For the Rotterdam Study-I and Rotterdam Study-II, the GWAS was funded by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture, and Science, the Ministry for Health, Welfare, and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The Erasmus Computing Grid, Rotterdam (The Netherlands) and the national German MediGRID and <email>Services@MediGRID</email> part of the German D-Grid were both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and # 01 IG 07015 G, for access to their grid resources. A Dehghan is supported by NWO grant (vici, 918-76-619). The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net of the University of Greifswald, Germany, funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the ‘Center of Knowledge Interchange’ program of the Siemens AG. The Vis study was supported through the grants from the Medical Research Council UK to H Campbell, AF Wright, and I Rudan; and Ministry of Science, Education, and Sport of the Republic of Croatia to I Rudan (number 108-1080315-0302) and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). The WGHS is supported by HL 043851 and HL69757 from the National Heart, Lung, and Blood Institute and CA 047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. The 3 City Study was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille and the Centre National de Génotypage. The 3 City Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM “Cohortes et collections de données biologiques” programme. Lille Génopôle received an unconditional grant from Eisai. The Blue Mountains Eye Study (BMES) has been supported by the Australian RADGAC grant (1992–94) and Australian National Health and Medical Research Council, Canberra Australia (Grant Nos: 974159, 211069, 991407, 457349). The GWAS studies of BMES population are supported by the Australian National Health and Medical Research Council (Grant Nos: 512423, 475604, 529912) and the Wellcome Trust, UK (2008), as part of Wellcome Trust Case Control Consortium 2 (A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster, grant numbers 085475/B/08/Z and 085475/08/Z). EG Holliday and JJ Wang are funded by the Australian National Health and Medical Research Council Fellowship Schemes. The CoLaus study received financial contributions from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (33CSCO-122661). M Bochud is supported by the Swiss School of Public Health Plus (SSPH+). The Cardiovascular Risk in Young Finns study (YFS) is supported by the Academy of Finland (grant no. 117797, 121584, and 126925), the Social Insurance Institution of Finland, University Hospital Medical funds to Tampere and Turku University Hospitals, and the Finnish Foundation of Cardiovascular Research. The Emil Aaaltonen Foundation (T Lehtimäki). EGCUT received support from FP7 grants ((201413 ENGAGE, 212111 BBMRI, 205419 ECOGENE, 245536 OPENGENE) and also received targeted financing from Estonian Government SF0180142s08 and from the European Union through the European Regional Development Fund, in the frame of Centre of Excellence in Genomics. The research of the FamHS-II was conducted in part using data and resources from the NHLBI Family Heart Study supported in part by NIH grant 5R01HL08770002. For the GoDARTs study, the Wellcome Trust provides support for Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection and the informatics support is provided by the Chief Scientist Office, and the Wellcome Trust funded Scottish Health Informatics Programme (SHIP). The INGI-Carlantino and INGI-FVG studies were supported by grants from Telethon, FVG region, and Fondo Trieste. The INGI-Cilento study was supported by grants from the EU (Vasoplus-037254), the Italian Ministry of Universities (FIRB -RBIN064YAT), the Assessorato Ricerca Regione Campania, the Ente Parco Nazionale del Cilento e Vallo di Diano, and the Fondazione Banco di Napoli to M Ciullo. The INGI – Val Borbera Study was supported from Compagnia di San Paolo, Torino, Italy, the Cariplo Fundation, Milano, Italy, and Italian Ministry of Health Progetto Finalizzato 2007 and 2009. The JUPITER trial and the genotyping were supported by AstraZeneca. The Ogliastra Genetic Park (OGP) - Replication Study and OGP - Talana study were supported by grants from the Italian Ministry of Education, University, and Research (MIUR) no. 5571/DSPAR/2002 and (FIRB) D. M. no. 718/Ric/2005. The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial was supported by an investigator initiated grant from Bristol-Myers Squibb, USA. The study was conducted, analyzed, and reported independently of the company. The SAPALDIA study was supported by the Swiss National Science Foundation (grants no 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099), the Federal Office for Forest, Environment, and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Zurich, the Swiss Lung League, the canton's Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticino, and Zurich. The SAPHIR-study was partially supported by a grant from the Kamillo Eisner Stiftung to B Paulweber and by grants from the “Genomics of Lipid-associated Disorders – GOLD” of the “Austrian Genome Research Programme GEN-AU” to F Kronenberg. eQTL analysis: HJ Gierman received support from the AFAR/EMF postdoctoral fellowship and the Stanford Dean's postdoctoral fellowship. 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