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La maladie de Parkinson en France (serveur d'exploration)

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Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease

Identifieur interne : 000346 ( Pmc/Checkpoint ); précédent : 000345; suivant : 000347

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease

Auteurs : Mike A. Nalls [États-Unis] ; Nathan Pankratz [États-Unis] ; Christina M. Lill [Allemagne] ; Chuong B. Do [États-Unis] ; Dena G. Hernandez [États-Unis] ; Mohamad Saad [États-Unis, France] ; Anita L. Destefano [États-Unis] ; Eleanna Kara [Royaume-Uni] ; Jose Bras [Royaume-Uni] ; Manu Sharma [Allemagne] ; Claudia Schulte [Allemagne] ; Margaux F. Keller [États-Unis] ; Sampath Arepalli [États-Unis] ; Christopher Letson [États-Unis] ; Connor Edsall [États-Unis] ; Hreinn Stefansson [Islande] ; Xinmin Liu [États-Unis] ; Hannah Pliner [États-Unis] ; Joseph H. Lee [États-Unis] ; Rong Cheng [États-Unis] ; M. Arfan Ikram [Pays-Bas] ; John P. A. Ioannidis [États-Unis] ; Georgios M. Hadjigeorgiou [Grèce] ; Joshua C. Bis [États-Unis] ; Maria Martinez [France] ; Joel S. Perlmutter [États-Unis] ; Alison Goate [États-Unis] ; Karen Marder [États-Unis] ; Brian Fiske [États-Unis] ; Margaret Sutherland [États-Unis] ; Georgia Xiromerisiou [Grèce] ; Richard H. Myers [États-Unis] ; Lorraine N. Clark [États-Unis] ; Kari Stefansson [Islande] ; John A. Hardy ; Peter Heutink [Allemagne] ; Honglei Chen [États-Unis] ; Nicholas W. Wood [Royaume-Uni] ; Henry Houlden [Royaume-Uni] ; Haydeh Payami [États-Unis] ; Alexis Brice [France] ; William K. Scott [États-Unis] ; Thomas Gasser [Allemagne] ; Lars Bertram [Allemagne] ; Nicholas Eriksson [États-Unis] ; Tatiana Foroud [États-Unis] ; Andrew B. Singleton [États-Unis]

Source :

RBID : PMC:4146673

Abstract

We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including GBA, GAK/DGKQ, SNCA, and HLA contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30; p-value = 2×10−16). We also show 6 risk loci associated with proximal gene expression or DNA methylation.


Url:
DOI: 10.1038/ng.3043
PubMed: 25064009
PubMed Central: 4146673


Affiliations:

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PMC:4146673

Le document en format XML

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<name sortKey="Pliner, Hannah" sort="Pliner, Hannah" uniqKey="Pliner H" first="Hannah" last="Pliner">Hannah Pliner</name>
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<name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name>
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<nlm:aff id="A23">Stanford Prevention Research Center, Stanford University, Stanford, USA</nlm:aff>
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<name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name>
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<name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name>
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<nlm:aff id="A25">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA</nlm:aff>
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<name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
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<nlm:aff id="A9">Paul Sabatier University, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Paul Sabatier University, Toulouse</wicri:regionArea>
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<region type="region">Occitanie (région administrative)</region>
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<settlement type="city">Toulouse</settlement>
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<author>
<name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name>
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<nlm:aff id="A26">Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
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<wicri:cityArea>Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis</wicri:cityArea>
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<nlm:aff id="A27">Department of Radiology, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Radiology, Washington University School of Medicine, St Louis</wicri:cityArea>
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<affiliation wicri:level="2">
<nlm:aff id="A28">Department of Neurology, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
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<wicri:cityArea>Department of Neurology, Washington University School of Medicine, St Louis</wicri:cityArea>
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<region type="state">Missouri (État)</region>
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<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
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<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
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<name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
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<region type="state">État de New York</region>
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<region type="state">État de New York</region>
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<affiliation>
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<wicri:noCountry code="subfield">Columbia University Medical Center. New York</wicri:noCountry>
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<affiliation>
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<wicri:noCountry code="subfield">Columbia University Medical Center. New York</wicri:noCountry>
</affiliation>
</author>
<author>
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<region type="state">État de New York</region>
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<region type="state">Maryland</region>
</placeName>
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<author>
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<wicri:regionArea>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly</wicri:regionArea>
<wicri:noRegion>University of Thessaly</wicri:noRegion>
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<affiliation wicri:level="1">
<nlm:aff id="A36">Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Department of Neurology, Papageorgiou Hospital, Thessaloniki</wicri:regionArea>
<wicri:noRegion>Thessaloniki</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name>
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<nlm:aff id="A10">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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</affiliation>
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<author>
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<nlm:aff id="A17">Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology and Cell Biology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A18">The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York</wicri:cityArea>
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<wicri:regionArea>deCODE genetics, Sturlugata 8, IS-101, Reykjavík</wicri:regionArea>
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<nlm:aff id="A6">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, United Kingdom, WC1N 3BG</nlm:aff>
<wicri:noCountry code="subfield">WC1N 3BG</wicri:noCountry>
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<name sortKey="Chen, Honglei" sort="Chen, Honglei" uniqKey="Chen H" first="Honglei" last="Chen">Honglei Chen</name>
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<nlm:aff id="A38">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Caroline du Nord</region>
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<name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W." last="Wood">Nicholas W. Wood</name>
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<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
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<name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name>
<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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</affiliation>
</author>
<author>
<name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name>
<affiliation wicri:level="2">
<nlm:aff id="A39">New York State Department of Health Wadsworth Center, Albany, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>New York State Department of Health Wadsworth Center, Albany, NY</wicri:regionArea>
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<region type="state">État de New York</region>
</placeName>
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<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation wicri:level="3">
<nlm:aff id="A41">Centre National de la Recherche Scientifique, UMR 7225, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique, UMR 7225, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<nlm:aff id="A42">AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<author>
<name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K" last="Scott">William K. Scott</name>
<affiliation wicri:level="1">
<nlm:aff id="A43">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville TN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville TN</wicri:regionArea>
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<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
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<nlm:aff id="A15">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen</wicri:regionArea>
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<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name>
<affiliation wicri:level="3">
<nlm:aff id="A3">Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin</wicri:regionArea>
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<nlm:aff id="A5">23andMe, Inc., Mountain View, California, USA</nlm:aff>
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<region type="state">Californie</region>
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<name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<affiliation wicri:level="2">
<nlm:aff id="A44">Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Indiana</region>
</placeName>
<wicri:cityArea>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis</wicri:cityArea>
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</author>
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<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
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<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
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<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
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<title xml:lang="en" level="a" type="main">Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease</title>
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<name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A" last="Nalls">Mike A. Nalls</name>
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<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
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<name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name>
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<nlm:aff id="A2">Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis</wicri:cityArea>
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<name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M." last="Lill">Christina M. Lill</name>
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<nlm:aff id="A3">Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany</nlm:aff>
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<nlm:aff id="A4">Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz</wicri:regionArea>
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<region type="land" nuts="2">Rhénanie-Palatinat</region>
<settlement type="city">Mayence</settlement>
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<name sortKey="Do, Chuong B" sort="Do, Chuong B" uniqKey="Do C" first="Chuong B" last="Do">Chuong B. Do</name>
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<nlm:aff id="A5">23andMe, Inc., Mountain View, California, USA</nlm:aff>
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<name sortKey="Hernandez, Dena G" sort="Hernandez, Dena G" uniqKey="Hernandez D" first="Dena G." last="Hernandez">Dena G. Hernandez</name>
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<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Maryland</region>
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</affiliation>
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<name sortKey="Saad, Mohamad" sort="Saad, Mohamad" uniqKey="Saad M" first="Mohamad" last="Saad">Mohamad Saad</name>
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<nlm:aff id="A7">Department of Biostatistics, University of Washington, Seattle, WA 8195-9460</nlm:aff>
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<settlement type="city">Seattle</settlement>
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<wicri:regionArea>Institut National de la Sante et de la Recherche Medicale, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse</wicri:regionArea>
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<region type="region">Occitanie (région administrative)</region>
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<nlm:aff id="A9">Paul Sabatier University, Toulouse, France</nlm:aff>
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<wicri:regionArea>Paul Sabatier University, Toulouse</wicri:regionArea>
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<region type="region">Occitanie (région administrative)</region>
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<name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
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<nlm:aff id="A10">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
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<region type="state">Massachusetts</region>
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<nlm:aff id="A11">Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA</nlm:aff>
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<region type="state">Massachusetts</region>
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<nlm:aff id="A12">NHLBI’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
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<region type="state">Massachusetts</region>
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<name sortKey="Kara, Eleanna" sort="Kara, Eleanna" uniqKey="Kara E" first="Eleanna" last="Kara">Eleanna Kara</name>
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<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
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<name sortKey="Bras, Jose" sort="Bras, Jose" uniqKey="Bras J" first="Jose" last="Bras">Jose Bras</name>
<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name>
<affiliation wicri:level="1">
<nlm:aff id="A14">Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tubingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tubingen</wicri:regionArea>
<wicri:noRegion>Tubingen</wicri:noRegion>
<wicri:noRegion>Tubingen</wicri:noRegion>
<wicri:noRegion>Tubingen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A15">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen</wicri:regionArea>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Schulte, Claudia" sort="Schulte, Claudia" uniqKey="Schulte C" first="Claudia" last="Schulte">Claudia Schulte</name>
<affiliation wicri:level="1">
<nlm:aff id="A15">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen</wicri:regionArea>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Keller, Margaux F" sort="Keller, Margaux F" uniqKey="Keller M" first="Margaux F." last="Keller">Margaux F. Keller</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Arepalli, Sampath" sort="Arepalli, Sampath" uniqKey="Arepalli S" first="Sampath" last="Arepalli">Sampath Arepalli</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Letson, Christopher" sort="Letson, Christopher" uniqKey="Letson C" first="Christopher" last="Letson">Christopher Letson</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Edsall, Connor" sort="Edsall, Connor" uniqKey="Edsall C" first="Connor" last="Edsall">Connor Edsall</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Stefansson, Hreinn" sort="Stefansson, Hreinn" uniqKey="Stefansson H" first="Hreinn" last="Stefansson">Hreinn Stefansson</name>
<affiliation wicri:level="1">
<nlm:aff id="A16">deCODE genetics, Sturlugata 8, IS-101, Reykjavík, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE genetics, Sturlugata 8, IS-101, Reykjavík</wicri:regionArea>
<wicri:noRegion>Reykjavík</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Xinmin" sort="Liu, Xinmin" uniqKey="Liu X" first="Xinmin" last="Liu">Xinmin Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="A17">Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology and Cell Biology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Pliner, Hannah" sort="Pliner, Hannah" uniqKey="Pliner H" first="Hannah" last="Pliner">Hannah Pliner</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Lee, Joseph H" sort="Lee, Joseph H" uniqKey="Lee J" first="Joseph H." last="Lee">Joseph H. Lee</name>
<affiliation wicri:level="2">
<nlm:aff id="A18">The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Cheng, Rong" sort="Cheng, Rong" uniqKey="Cheng R" first="Rong" last="Cheng">Rong Cheng</name>
<affiliation wicri:level="2">
<nlm:aff id="A18">The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M. Arfan" last="Ikram">M. Arfan Ikram</name>
<affiliation wicri:level="3">
<nlm:aff id="A20">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName>
<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A21">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName>
<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName>
<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Stanford Prevention Research Center, Stanford University, Stanford, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stanford Prevention Research Center, Stanford University, Stanford</wicri:regionArea>
<wicri:noRegion>Stanford</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly</wicri:regionArea>
<wicri:noRegion>University of Thessaly</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name>
<affiliation wicri:level="2">
<nlm:aff id="A25">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
<affiliation wicri:level="3">
<nlm:aff id="A8">Institut National de la Sante et de la Recherche Medicale, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Sante et de la Recherche Medicale, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse</wicri:regionArea>
<placeName>
<region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A9">Paul Sabatier University, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Paul Sabatier University, Toulouse</wicri:regionArea>
<placeName>
<region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name>
<affiliation wicri:level="2">
<nlm:aff id="A26">Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A27">Department of Radiology, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Radiology, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A28">Department of Neurology, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Neurology, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<affiliation wicri:level="2">
<nlm:aff id="A26">Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A28">Department of Neurology, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Neurology, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A29">Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Psychiatry, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A30">Department of Genetics, Washington University School of Medicine, St Louis, MO 63110</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Genetics, Washington University School of Medicine, St Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<affiliation wicri:level="2">
<nlm:aff id="A18">The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A31">Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Gertrude H. Sergievsky Center, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="A32">Department of Neurology, Columbia University Medical Center. New York</nlm:aff>
<wicri:noCountry code="subfield">Columbia University Medical Center. New York</wicri:noCountry>
</affiliation>
<affiliation>
<nlm:aff id="A33">Department of Psychiatry, Columbia University Medical Center. New York</nlm:aff>
<wicri:noCountry code="subfield">Columbia University Medical Center. New York</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Fiske, Brian" sort="Fiske, Brian" uniqKey="Fiske B" first="Brian" last="Fiske">Brian Fiske</name>
<affiliation wicri:level="2">
<nlm:aff id="A34">The Michael J. Fox Foundation for Parkinson’s Research, New York, NY</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Michael J. Fox Foundation for Parkinson’s Research, New York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Sutherland, Margaret" sort="Sutherland, Margaret" uniqKey="Sutherland M" first="Margaret" last="Sutherland">Margaret Sutherland</name>
<affiliation wicri:level="2">
<nlm:aff id="A35">Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly</wicri:regionArea>
<wicri:noRegion>University of Thessaly</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A36">Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Department of Neurology, Papageorgiou Hospital, Thessaloniki</wicri:regionArea>
<wicri:noRegion>Thessaloniki</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name>
<affiliation wicri:level="2">
<nlm:aff id="A10">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine N" last="Clark">Lorraine N. Clark</name>
<affiliation wicri:level="2">
<nlm:aff id="A17">Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology and Cell Biology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A18">The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name>
<affiliation wicri:level="1">
<nlm:aff id="A16">deCODE genetics, Sturlugata 8, IS-101, Reykjavík, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE genetics, Sturlugata 8, IS-101, Reykjavík</wicri:regionArea>
<wicri:noRegion>Reykjavík</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hardy, John A" sort="Hardy, John A" uniqKey="Hardy J" first="John A." last="Hardy">John A. Hardy</name>
<affiliation>
<nlm:aff id="A6">Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, United Kingdom, WC1N 3BG</nlm:aff>
<wicri:noCountry code="subfield">WC1N 3BG</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
<affiliation wicri:level="3">
<nlm:aff id="A37">Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Tübingen</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chen, Honglei" sort="Chen, Honglei" uniqKey="Chen H" first="Honglei" last="Chen">Honglei Chen</name>
<affiliation wicri:level="2">
<nlm:aff id="A38">Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W." last="Wood">Nicholas W. Wood</name>
<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name>
<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</nlm:aff>
<orgName type="university">University College de Londres</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name>
<affiliation wicri:level="2">
<nlm:aff id="A39">New York State Department of Health Wadsworth Center, Albany, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>New York State Department of Health Wadsworth Center, Albany, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation wicri:level="3">
<nlm:aff id="A41">Centre National de la Recherche Scientifique, UMR 7225, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique, UMR 7225, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A42">AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K" last="Scott">William K. Scott</name>
<affiliation wicri:level="1">
<nlm:aff id="A43">Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville TN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville TN</wicri:regionArea>
<wicri:noRegion>Nashville TN</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation wicri:level="1">
<nlm:aff id="A15">Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen</wicri:regionArea>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
<wicri:noRegion>University of Tübingen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name>
<affiliation wicri:level="3">
<nlm:aff id="A3">Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin</wicri:regionArea>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Eriksson, Nicholas" sort="Eriksson, Nicholas" uniqKey="Eriksson N" first="Nicholas" last="Eriksson">Nicholas Eriksson</name>
<affiliation wicri:level="2">
<nlm:aff id="A5">23andMe, Inc., Mountain View, California, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Inc., Mountain View, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<affiliation wicri:level="2">
<nlm:aff id="A44">Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Indiana</region>
</placeName>
<wicri:cityArea>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nature genetics</title>
<idno type="ISSN">1061-4036</idno>
<idno type="eISSN">1546-1718</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P1">We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including
<italic>GBA</italic>
,
<italic>GAK/DGKQ</italic>
,
<italic>SNCA</italic>
, and
<italic>HLA</italic>
contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30; p-value = 2×10
<sup>−16</sup>
). We also show 6 risk loci associated with proximal gene expression or DNA methylation.</p>
</div>
</front>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">9216904</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2419</journal-id>
<journal-id journal-id-type="nlm-ta">Nat Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id>
<journal-title-group>
<journal-title>Nature genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1061-4036</issn>
<issn pub-type="epub">1546-1718</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25064009</article-id>
<article-id pub-id-type="pmc">4146673</article-id>
<article-id pub-id-type="doi">10.1038/ng.3043</article-id>
<article-id pub-id-type="manuscript">NIHMS610183</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Nalls</surname>
<given-names>Mike A</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN2" ref-type="author-notes">#</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pankratz</surname>
<given-names>Nathan</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref rid="FN2" ref-type="author-notes">#</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lill</surname>
<given-names>Christina M.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Do</surname>
<given-names>Chuong B</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hernandez</surname>
<given-names>Dena G.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Saad</surname>
<given-names>Mohamad</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>DeStefano</surname>
<given-names>Anita L.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="aff" rid="A11">11</xref>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kara</surname>
<given-names>Eleanna</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bras</surname>
<given-names>Jose</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sharma</surname>
<given-names>Manu</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schulte</surname>
<given-names>Claudia</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Keller</surname>
<given-names>Margaux F.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Arepalli</surname>
<given-names>Sampath</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Letson</surname>
<given-names>Christopher</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Edsall</surname>
<given-names>Connor</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stefansson</surname>
<given-names>Hreinn</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Xinmin</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pliner</surname>
<given-names>Hannah</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Joseph H.</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cheng</surname>
<given-names>Rong</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<collab>International Parkinson’s Disease Genomics Consortium (IPDGC)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Parkinson’s Study Group (PSG) Parkinson’s Research: The Organized GENetics Initiative (PROGENI)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>23andMe</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Gene PD</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>NeuroGenetics Research Consortium (NGRC)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Hussman Institute of Human Genomics (HIHG)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>The Ashkenazi Jewish Dataset Investigator</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>North American Brain Expression Consortium (NABEC)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>United Kingdom Brain Expression Consortium (UKBEC)</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Greek Parkinson’s Disease Consortium</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<collab>Alzheimer Genetic Analysis Group</collab>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ikram</surname>
<given-names>M. Arfan</given-names>
</name>
<xref ref-type="aff" rid="A20">20</xref>
<xref ref-type="aff" rid="A21">21</xref>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ioannidis</surname>
<given-names>John P.A.</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hadjigeorgiou</surname>
<given-names>Georgios M.</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bis</surname>
<given-names>Joshua C.</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Martinez</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Perlmutter</surname>
<given-names>Joel S.</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
<xref ref-type="aff" rid="A27">27</xref>
<xref ref-type="aff" rid="A28">28</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Goate</surname>
<given-names>Alison</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
<xref ref-type="aff" rid="A28">28</xref>
<xref ref-type="aff" rid="A29">29</xref>
<xref ref-type="aff" rid="A30">30</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marder</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
<xref ref-type="aff" rid="A31">31</xref>
<xref ref-type="aff" rid="A32">32</xref>
<xref ref-type="aff" rid="A33">33</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fiske</surname>
<given-names>Brian</given-names>
</name>
<xref ref-type="aff" rid="A34">34</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sutherland</surname>
<given-names>Margaret</given-names>
</name>
<xref ref-type="aff" rid="A35">35</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Xiromerisiou</surname>
<given-names>Georgia</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
<xref ref-type="aff" rid="A36">36</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Myers</surname>
<given-names>Richard H.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Clark</surname>
<given-names>Lorraine N</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stefansson</surname>
<given-names>Kari</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hardy</surname>
<given-names>John A.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Heutink</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="A37">37</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Honglei</given-names>
</name>
<xref ref-type="aff" rid="A38">38</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wood</surname>
<given-names>Nicholas W.</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Houlden</surname>
<given-names>Henry</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Payami</surname>
<given-names>Haydeh</given-names>
</name>
<xref ref-type="aff" rid="A39">39</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Brice</surname>
<given-names>Alexis</given-names>
</name>
<xref ref-type="aff" rid="A41">41</xref>
<xref ref-type="aff" rid="A42">42</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scott</surname>
<given-names>William K</given-names>
</name>
<xref ref-type="aff" rid="A43">43</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gasser</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bertram</surname>
<given-names>Lars</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eriksson</surname>
<given-names>Nicholas</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Foroud</surname>
<given-names>Tatiana</given-names>
</name>
<xref ref-type="aff" rid="A44">44</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Singleton</surname>
<given-names>Andrew B.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892</aff>
<aff id="A2">
<label>2</label>
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455</aff>
<aff id="A3">
<label>3</label>
Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany</aff>
<aff id="A4">
<label>4</label>
Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany</aff>
<aff id="A5">
<label>5</label>
23andMe, Inc., Mountain View, California, USA</aff>
<aff id="A6">
<label>6</label>
Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, United Kingdom, WC1N 3BG</aff>
<aff id="A7">
<label>7</label>
Department of Biostatistics, University of Washington, Seattle, WA 8195-9460</aff>
<aff id="A8">
<label>8</label>
Institut National de la Sante et de la Recherche Medicale, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France</aff>
<aff id="A9">
<label>9</label>
Paul Sabatier University, Toulouse, France</aff>
<aff id="A10">
<label>10</label>
Department of Neurology, Boston University School of Medicine, Boston, MA, USA</aff>
<aff id="A11">
<label>11</label>
Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA</aff>
<aff id="A12">
<label>12</label>
NHLBI’s Framingham Heart Study, Framingham, MA, USA</aff>
<aff id="A13">
<label>13</label>
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom, WC1N 3BG</aff>
<aff id="A14">
<label>14</label>
Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tubingen, Germany</aff>
<aff id="A15">
<label>15</label>
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany</aff>
<aff id="A16">
<label>16</label>
deCODE genetics, Sturlugata 8, IS-101, Reykjavík, Iceland</aff>
<aff id="A17">
<label>17</label>
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032</aff>
<aff id="A18">
<label>18</label>
The Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, new York, NY 10032</aff>
<aff id="A19">
<label>19</label>
A full list of investigators is in the
<xref rid="SD1" ref-type="supplementary-material">Supplementary Note</xref>
</aff>
<aff id="A20">
<label>20</label>
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</aff>
<aff id="A21">
<label>21</label>
Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</aff>
<aff id="A22">
<label>22</label>
Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands</aff>
<aff id="A23">
<label>23</label>
Stanford Prevention Research Center, Stanford University, Stanford, USA</aff>
<aff id="A24">
<label>24</label>
Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Greece</aff>
<aff id="A25">
<label>25</label>
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA</aff>
<aff id="A26">
<label>26</label>
Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110</aff>
<aff id="A27">
<label>27</label>
Department of Radiology, Washington University School of Medicine, St Louis, MO 63110</aff>
<aff id="A28">
<label>28</label>
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110</aff>
<aff id="A29">
<label>29</label>
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110</aff>
<aff id="A30">
<label>30</label>
Department of Genetics, Washington University School of Medicine, St Louis, MO 63110</aff>
<aff id="A31">
<label>31</label>
Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032</aff>
<aff id="A32">
<label>32</label>
Department of Neurology, Columbia University Medical Center. New York</aff>
<aff id="A33">
<label>33</label>
Department of Psychiatry, Columbia University Medical Center. New York</aff>
<aff id="A34">
<label>34</label>
The Michael J. Fox Foundation for Parkinson’s Research, New York, NY</aff>
<aff id="A35">
<label>35</label>
Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892</aff>
<aff id="A36">
<label>36</label>
Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece</aff>
<aff id="A37">
<label>37</label>
Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany</aff>
<aff id="A38">
<label>38</label>
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina</aff>
<aff id="A39">
<label>39</label>
New York State Department of Health Wadsworth Center, Albany, NY, USA</aff>
<aff id="A40">
<label>40</label>
Université Pierre et Marie Curie-Paris, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, UMR-S975, Paris, France</aff>
<aff id="A41">
<label>41</label>
Centre National de la Recherche Scientifique, UMR 7225, Paris, France</aff>
<aff id="A42">
<label>42</label>
AP-HP, Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France</aff>
<aff id="A43">
<label>43</label>
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville TN, USA</aff>
<aff id="A44">
<label>44</label>
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
Address for correspondence:
<email>singleta@mail.nih.gov</email>
</corresp>
<fn id="FN2">
<label>#</label>
<p>Denotes shared authorship.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>1</day>
<month>7</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>27</day>
<month>7</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<month>9</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>3</month>
<year>2015</year>
</pub-date>
<volume>46</volume>
<issue>9</issue>
<fpage>989</fpage>
<lpage>993</lpage>
<pmc-comment>elocation-id from pubmed: 10.1038/ng.3043</pmc-comment>
<permissions>
<license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">
<license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link>
</license-p>
</license>
</permissions>
<abstract>
<p id="P1">We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including
<italic>GBA</italic>
,
<italic>GAK/DGKQ</italic>
,
<italic>SNCA</italic>
, and
<italic>HLA</italic>
contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30; p-value = 2×10
<sup>−16</sup>
). We also show 6 risk loci associated with proximal gene expression or DNA methylation.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="F1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>Manhattan plot of discovery phase meta-analyses.</p>
</caption>
<graphic xlink:href="nihms610183f1"></graphic>
</fig>
<fig id="F2" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p>Forest plots describing cohort level and summary effects of risk profile analyses.</p>
</caption>
<graphic xlink:href="nihms610183f2"></graphic>
</fig>
<table-wrap id="T1" position="float" orientation="landscape">
<label>Table 1</label>
<caption>
<p>Results of discovery and replication association analyses.</p>
</caption>
<table frame="above" rules="groups">
<thead>
<tr>
<th colspan="7" valign="middle" align="center" rowspan="1">SNP Information</th>
<th colspan="2" valign="middle" align="center" rowspan="1">Discovery phase (13,728 cases and 95,282 controls)</th>
<th colspan="2" valign="middle" align="center" rowspan="1">Replication phase (5,353 cases and 5,551 controls)</th>
<th colspan="2" valign="middle" align="center" rowspan="1">Joint phase (19,081 cases and 100,833 controls)</th>
</tr>
<tr>
<th colspan="13" valign="bottom" align="left" rowspan="1">
<hr></hr>
</th>
</tr>
<tr>
<th valign="middle" align="center" rowspan="1" colspan="1">SNP</th>
<th valign="middle" align="center" rowspan="1" colspan="1">C</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Position (bp)</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Nearest gene(s)</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Effect allele</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Alternate allele</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Effect allele frequency</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Odds ratio</th>
<th valign="middle" align="center" rowspan="1" colspan="1">P</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Odds ratio</th>
<th valign="middle" align="center" rowspan="1" colspan="1">P</th>
<th valign="middle" align="center" rowspan="1" colspan="1">Odds ratio</th>
<th valign="middle" align="center" rowspan="1" colspan="1">P</th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="13" align="center" valign="middle" rowspan="1">Genome Wide Significant, Discovery Phase</td>
</tr>
<tr>
<td colspan="13" valign="bottom" align="left" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs35749011
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">155,135,036</td>
<td align="center" valign="middle" rowspan="1" colspan="1">GBA/SYT11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.017</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.762</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.09×10-23</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.307</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.48×10-09</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.824</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.37×-29</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs823118</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">205,723,572</td>
<td align="center" valign="middle" rowspan="1" colspan="1">RAB7L1/NUCKS1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.559</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.126</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.36×10-13</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.109</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.43×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.122</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.66×-16</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs10797576</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">232,664,611</td>
<td align="center" valign="middle" rowspan="1" colspan="1">SIPA1L2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.14</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.139</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.19×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.38×10-03</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.131</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.87×-10</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs6430538</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">135,539,967</td>
<td align="center" valign="middle" rowspan="1" colspan="1">ACMSD/TMEM163</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.43</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.873</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.56×10-15</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.882</td>
<td align="center" valign="middle" rowspan="1" colspan="1">9.42×10-06</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.875</td>
<td align="center" valign="middle" rowspan="1" colspan="1">9.13×-20</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs1474055
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">169,110,394</td>
<td align="center" valign="middle" rowspan="1" colspan="1">STK39</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.128</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.213</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.12×10-16</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.218</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.07×10-06</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.214</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.15×-20</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs115185635
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3</td>
<td align="center" valign="middle" rowspan="1" colspan="1">87,520,857</td>
<td align="center" valign="middle" rowspan="1" colspan="1">KRT8P25/APOOP2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.035</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.789</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.18×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.931</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.846</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.142</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.022</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs12637471</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3</td>
<td align="center" valign="middle" rowspan="1" colspan="1">182,762,437</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MCCC1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.193</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.844</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.32×10-16</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.836</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.72×10-07</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.842</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.14×-21</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs34311866</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4</td>
<td align="center" valign="middle" rowspan="1" colspan="1">951,947</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TMEM175/GAK/DGKQ</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.809</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.784</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.58×10-33</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.791</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.29×10-12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.786</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.02×-43</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs11724635</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4</td>
<td align="center" valign="middle" rowspan="1" colspan="1">15,737,101</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BST1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.553</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.122</td>
<td align="center" valign="middle" rowspan="1" colspan="1">8.07×10-13</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.138</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.73×10-06</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.126</td>
<td align="center" valign="middle" rowspan="1" colspan="1">9.44×-18</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs6812193</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4</td>
<td align="center" valign="middle" rowspan="1" colspan="1">77,198,986</td>
<td align="center" valign="middle" rowspan="1" colspan="1">FAM47E/SCARB2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.364</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.897</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.17×10-11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.935</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.011</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.907</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.95×-11</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs356182</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4</td>
<td align="center" valign="middle" rowspan="1" colspan="1">90,626,111</td>
<td align="center" valign="middle" rowspan="1" colspan="1">SNCA</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.633</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.737</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.23×10-67</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.822</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.75×10-12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.760</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.16×-73</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs9275326
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6</td>
<td align="center" valign="middle" rowspan="1" colspan="1">32,666,660</td>
<td align="center" valign="middle" rowspan="1" colspan="1">HLA-DQB1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.094</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.797</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.82×10-13</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.9</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.018</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.826</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.19×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs199347</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7</td>
<td align="center" valign="middle" rowspan="1" colspan="1">23,293,746</td>
<td align="center" valign="middle" rowspan="1" colspan="1">GPNMB</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.59</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.123</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.37×10-12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.072</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.66×10-03</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.110</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.18×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs117896735
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">10</td>
<td align="center" valign="middle" rowspan="1" colspan="1">121,536,327</td>
<td align="center" valign="middle" rowspan="1" colspan="1">INPP5F</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.014</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.767</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.21×10-11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.404</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.10×10-03</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.624</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.34×-13</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs3793947
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">83,544,472</td>
<td align="center" valign="middle" rowspan="1" colspan="1">DLG2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.443</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.912</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.59×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.976</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.201</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.929</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.96×-07</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs329648</td>
<td align="center" valign="middle" rowspan="1" colspan="1">11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">133,765,367</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MIR4697</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.354</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.65×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.121</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.38×10-05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.105</td>
<td align="center" valign="middle" rowspan="1" colspan="1">9.83×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs76904798</td>
<td align="center" valign="middle" rowspan="1" colspan="1">12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">40,614,434</td>
<td align="center" valign="middle" rowspan="1" colspan="1">LRRK2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.143</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.17</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.33×10-12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.69×10-03</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.155</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.24×-14</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs11060180</td>
<td align="center" valign="middle" rowspan="1" colspan="1">12</td>
<td align="center" valign="middle" rowspan="1" colspan="1">123,303,586</td>
<td align="center" valign="middle" rowspan="1" colspan="1">CCDC62</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.558</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.101</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.14×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.114</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.26×10-05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.105</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.02×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs11158026</td>
<td align="center" valign="middle" rowspan="1" colspan="1">14</td>
<td align="center" valign="middle" rowspan="1" colspan="1">55,348,869</td>
<td align="center" valign="middle" rowspan="1" colspan="1">GCH1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.335</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.889</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.13×10-11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.948</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.039</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.904</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.85×-11</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs1555399
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">14</td>
<td align="center" valign="middle" rowspan="1" colspan="1">67,984,370</td>
<td align="center" valign="middle" rowspan="1" colspan="1">TMEM229B</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.468</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.872</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.53×10-16</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.971</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.144</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.897</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.63×-14</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs2414739</td>
<td align="center" valign="middle" rowspan="1" colspan="1">15</td>
<td align="center" valign="middle" rowspan="1" colspan="1">61,994,134</td>
<td align="center" valign="middle" rowspan="1" colspan="1">VPS13C</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.734</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.114</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.13×10-09</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.109</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.96×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.113</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.23×-11</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs14235</td>
<td align="center" valign="middle" rowspan="1" colspan="1">16</td>
<td align="center" valign="middle" rowspan="1" colspan="1">31,121,793</td>
<td align="center" valign="middle" rowspan="1" colspan="1">BCKDK/STX1B</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.381</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.094</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.89×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.133</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.72×10-06</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.103</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.43×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs17649553</td>
<td align="center" valign="middle" rowspan="1" colspan="1">17</td>
<td align="center" valign="middle" rowspan="1" colspan="1">43,994,648</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MAPT</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.226</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.771</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.86×10-37</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.764</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.03×10-15</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.769</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.37×-48</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs12456492</td>
<td align="center" valign="middle" rowspan="1" colspan="1">18</td>
<td align="center" valign="middle" rowspan="1" colspan="1">40,673,380</td>
<td align="center" valign="middle" rowspan="1" colspan="1">RIT2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.693</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.905</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.12×10-09</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.9</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.16×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.904</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.74×-12</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs62120679
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">19</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2,363,319</td>
<td align="center" valign="middle" rowspan="1" colspan="1">SPPL2B</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.314</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.141</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.53×10-09</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.999</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.518</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.097</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.57×-07</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs8118008
<xref rid="TFN2" ref-type="table-fn">*</xref>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">20</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3,168,166</td>
<td align="center" valign="middle" rowspan="1" colspan="1">DDRGK1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.657</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.111</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.32×10-08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.113</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.18×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.111</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.04×-11</td>
</tr>
<tr>
<td colspan="13" valign="bottom" align="left" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td colspan="13" align="center" valign="middle" rowspan="1">Previously Reported as Significant in Genome Wide Studies</td>
</tr>
<tr>
<td colspan="13" valign="bottom" align="left" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs34016896</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3</td>
<td align="center" valign="middle" rowspan="1" colspan="1">160,992,864</td>
<td align="center" valign="middle" rowspan="1" colspan="1">NMD3</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.319</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.08</td>
<td align="center" valign="middle" rowspan="1" colspan="1">7.68×10-06</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.028</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.174</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.067</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.08×-05</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs591323</td>
<td align="center" valign="middle" rowspan="1" colspan="1">8</td>
<td align="center" valign="middle" rowspan="1" colspan="1">16,697,091</td>
<td align="center" valign="middle" rowspan="1" colspan="1">FGF20</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.275</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.921</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.30×10-05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.902</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.16×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.916</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6.68×-08</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs60298754</td>
<td align="center" valign="middle" rowspan="1" colspan="1">8</td>
<td align="center" valign="middle" rowspan="1" colspan="1">89,373,041</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MMP16</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.024</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.078</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.181</td>
<td align="center" valign="middle" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" rowspan="1" colspan="1">-</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.078</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.181</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs7077361</td>
<td align="center" valign="middle" rowspan="1" colspan="1">10</td>
<td align="center" valign="middle" rowspan="1" colspan="1">15,561,543</td>
<td align="center" valign="middle" rowspan="1" colspan="1">ITGA8</td>
<td align="center" valign="middle" rowspan="1" colspan="1">t</td>
<td align="center" valign="middle" rowspan="1" colspan="1">c</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.874</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.11</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.24×10-05</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.044</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.154</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.092</td>
<td align="center" valign="middle" rowspan="1" colspan="1">4.16×-05</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs11868035</td>
<td align="center" valign="middle" rowspan="1" colspan="1">17</td>
<td align="center" valign="middle" rowspan="1" colspan="1">17,715,101</td>
<td align="center" valign="middle" rowspan="1" colspan="1">SREBF/RAI1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.298</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.937</td>
<td align="center" valign="middle" rowspan="1" colspan="1">2.17×10-04</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.947</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.036</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.939</td>
<td align="center" valign="middle" rowspan="1" colspan="1">5.98×-05</td>
</tr>
<tr>
<td align="center" valign="middle" rowspan="1" colspan="1">rs2823357</td>
<td align="center" valign="middle" rowspan="1" colspan="1">21</td>
<td align="center" valign="middle" rowspan="1" colspan="1">16,914,905</td>
<td align="center" valign="middle" rowspan="1" colspan="1">USP25</td>
<td align="center" valign="middle" rowspan="1" colspan="1">a</td>
<td align="center" valign="middle" rowspan="1" colspan="1">g</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.37</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.036</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.032</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.018</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.267</td>
<td align="center" valign="middle" rowspan="1" colspan="1">1.031</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.027</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN1">
<p>C - Chromosome; OR - odds ratio</p>
</fn>
<fn id="TFN2">
<label>*</label>
<p>replication genotyping for these SNPs failed assay design or quality control and a suitable proxy variant was selected (rs35749011, proxy rs71628662; rs1474055, proxy rs1955337; rs115185635, proxy rs62267708; rs117896735, proxy rs118117788; rs3793947, proxy rs12283611; rs1555399, proxy rs1077989; rs62120679, proxy rs10402629; rs8118008, proxy rs55785911). Note, only replication phase p-values are one-sided. Nearest gene or previously published proximal gene names included in table.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" position="float" orientation="landscape">
<label>Table 2</label>
<caption>
<p>Results of conditional association analyses.</p>
</caption>
<table frame="void" rules="none">
<tbody>
<tr>
<td align="left" valign="bottom" rowspan="1" colspan="1">Significant conditional SNP, signifiying secondary locus</td>
<td align="center" valign="bottom" rowspan="1" colspan="1"></td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs114138760</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs79217002</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs34884217</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs1596117*</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs7681154*</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs13201101*</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs10886515</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs117022814</td>
</tr>
<tr>
<td align="left" valign="bottom" rowspan="1" colspan="1">Most significant SNP from discovery phase, used as covariate</td>
<td align="center" valign="bottom" rowspan="1" colspan="1"></td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs35749011</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs12637471</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs34311866</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs6812193</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs356182</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs9275326</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs117896735</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">rs62120679</td>
</tr>
<tr>
<td align="left" valign="bottom" rowspan="1" colspan="1">Nearest gene(s)</td>
<td align="center" valign="bottom" rowspan="1" colspan="1"></td>
<td align="center" valign="bottom" rowspan="1" colspan="1">GBA/SYT11</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">MCCC1</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">TMEM175/GAK/DGKQ</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">FAM47E/SCARB2</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">SNCA</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">HLA-DQB1</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">INPP5F</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">SPPL2B</td>
</tr>
<tr>
<td align="left" valign="bottom" rowspan="1" colspan="1">R2 between SNPs based on 1000 Genomes Project European ancestry samples</td>
<td align="center" valign="bottom" rowspan="1" colspan="1"></td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.000</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.003</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.012</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.028</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.209</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.002</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.000</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.006</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="5" colspan="1">Conditional SNP information</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">C</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">3</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">4</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">4</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">4</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">6</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">10</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">19</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">Position (bp)</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">154898185</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">183011072</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">944210</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">77151490</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">90763703</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">32343604</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">121343589</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2209647</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">Effect allele</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">a</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">a</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">t</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">a</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">t</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">t</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">t</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">Alternate allele</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">g</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">g</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">c</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">Effect allele frequency</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.012</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.9907</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.9126</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.2005</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.5021</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.0529</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.7145</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.0262</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2" colspan="1">Summary statistics from conditional analyses</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">Odds ratio</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.574</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.669</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.247</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.115</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.841</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.192</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.100</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.341</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">P</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">3.80×10-07</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">9.31×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.10×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.80×10-07</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">7.09×10-19</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">3.84×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">9.19×10-07</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.95×10-06</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2" colspan="1">Summary statistics from discovery phase</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">Odds ratio</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.497</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.688</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.344</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.094</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.997</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.179</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.105</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.319</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">P</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.18×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.69×10-05</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.56×10-12</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">6.05×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.854</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">4.95×10-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.59×10-08</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.00×10-06</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2" colspan="1">Summary statistics from replicaiton phase</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">Odds ratio</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.586</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.076</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.105</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.036</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.934</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.217</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.023</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.094</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">P</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">5.72×10-04</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.714</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.017</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.189</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">8.02×10-03</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">8.33×10-03</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.234</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.174</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2" colspan="1">Summary statistics from combined discovery and replication phases</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">Odds ratio</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.519</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.789</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.232</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.083</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.981</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.185</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.084</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.255</td>
</tr>
<tr>
<td align="center" valign="bottom" rowspan="1" colspan="1">P</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">9.73×-09</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">1.08×-03</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.51×-11</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">9.45×-06</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">0.171</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.50×-07</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">2.26×-07</td>
<td align="center" valign="bottom" rowspan="1" colspan="1">4.82×-06</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN3">
<p>Replication genotyping for these SNPs failed assay design or quality control and a suitable proxy variant was selected (rs1596117, proxy rs4859430; rs7681154, proxy rs3910105; rs13201101, proxy rs8192591; based on discovery series comparison, the minor allele for rs3910105 tags the major allele of rs7681154 therefore risk is consistent across proxy and discovery SNP). Note, only replication phase p-values are one-sided. Nearest gene or previously published proximal gene names included in table.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>France</li>
<li>Grèce</li>
<li>Islande</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Bade-Wurtemberg</li>
<li>Berlin</li>
<li>Californie</li>
<li>Caroline du Nord</li>
<li>District de Tübingen</li>
<li>Grand Londres</li>
<li>Hollande-Méridionale</li>
<li>Indiana</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Midi-Pyrénées</li>
<li>Minnesota</li>
<li>Missouri (État)</li>
<li>Occitanie (région administrative)</li>
<li>Rhénanie-Palatinat</li>
<li>Washington (État)</li>
<li>État de New York</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Berlin</li>
<li>Londres</li>
<li>Mayence</li>
<li>Paris</li>
<li>Rotterdam</li>
<li>Seattle</li>
<li>Toulouse</li>
<li>Tübingen</li>
</settlement>
<orgName>
<li>University College de Londres</li>
<li>Université de Washington</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Hardy, John A" sort="Hardy, John A" uniqKey="Hardy J" first="John A." last="Hardy">John A. Hardy</name>
</noCountry>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A" last="Nalls">Mike A. Nalls</name>
</region>
<name sortKey="Arepalli, Sampath" sort="Arepalli, Sampath" uniqKey="Arepalli S" first="Sampath" last="Arepalli">Sampath Arepalli</name>
<name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name>
<name sortKey="Chen, Honglei" sort="Chen, Honglei" uniqKey="Chen H" first="Honglei" last="Chen">Honglei Chen</name>
<name sortKey="Cheng, Rong" sort="Cheng, Rong" uniqKey="Cheng R" first="Rong" last="Cheng">Rong Cheng</name>
<name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine N" last="Clark">Lorraine N. Clark</name>
<name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine N" last="Clark">Lorraine N. Clark</name>
<name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
<name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
<name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
<name sortKey="Do, Chuong B" sort="Do, Chuong B" uniqKey="Do C" first="Chuong B" last="Do">Chuong B. Do</name>
<name sortKey="Edsall, Connor" sort="Edsall, Connor" uniqKey="Edsall C" first="Connor" last="Edsall">Connor Edsall</name>
<name sortKey="Eriksson, Nicholas" sort="Eriksson, Nicholas" uniqKey="Eriksson N" first="Nicholas" last="Eriksson">Nicholas Eriksson</name>
<name sortKey="Fiske, Brian" sort="Fiske, Brian" uniqKey="Fiske B" first="Brian" last="Fiske">Brian Fiske</name>
<name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<name sortKey="Hernandez, Dena G" sort="Hernandez, Dena G" uniqKey="Hernandez D" first="Dena G." last="Hernandez">Dena G. Hernandez</name>
<name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name>
<name sortKey="Keller, Margaux F" sort="Keller, Margaux F" uniqKey="Keller M" first="Margaux F." last="Keller">Margaux F. Keller</name>
<name sortKey="Lee, Joseph H" sort="Lee, Joseph H" uniqKey="Lee J" first="Joseph H." last="Lee">Joseph H. Lee</name>
<name sortKey="Letson, Christopher" sort="Letson, Christopher" uniqKey="Letson C" first="Christopher" last="Letson">Christopher Letson</name>
<name sortKey="Liu, Xinmin" sort="Liu, Xinmin" uniqKey="Liu X" first="Xinmin" last="Liu">Xinmin Liu</name>
<name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name>
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