Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
Identifieur interne : 000024 ( PubMed/Curation ); précédent : 000023; suivant : 000025Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
Auteurs : Mike. Nalls [États-Unis] ; Nathan Pankratz [États-Unis] ; Christina. Lill [Allemagne] ; Chuong. Do [États-Unis] ; Dena. Hernandez [Royaume-Uni] ; Mohamad Saad [France] ; Anita. Destefano [États-Unis] ; Eleanna Kara [Royaume-Uni] ; Jose Bras [Royaume-Uni] ; Manu Sharma [Allemagne] ; Claudia Schulte [Allemagne] ; Margaux. 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. Lee [États-Unis] ; Rong Cheng [États-Unis] ; M Ikram [Pays-Bas] ; John. Ioannidis [États-Unis] ; Georgios. Hadjigeorgiou [Grèce] ; Joshua. Bis [États-Unis] ; Maria Martinez [France] ; Joel. Perlmutter [États-Unis] ; Alison Goate [États-Unis] ; Karen Marder [États-Unis] ; Brian Fiske [États-Unis] ; Margaret Sutherland [États-Unis] ; Georgia Xiromerisiou [Grèce] ; Richard. Myers [États-Unis] ; Lorraine. Clark [États-Unis] ; Kari Stefansson [Islande] ; John. Hardy [Royaume-Uni] ; Peter Heutink [Allemagne] ; Honglei Chen [États-Unis] ; Nicholas. Wood [Royaume-Uni] ; Henry Houlden [Royaume-Uni] ; Haydeh Payami [États-Unis] ; Alexis Brice [France] ; William. Scott [États-Unis] ; Thomas Gasser [Allemagne] ; Lars Bertram [Royaume-Uni] ; Nicholas Eriksson [États-Unis] ; Tatiana Foroud [États-Unis] ; Andrew. Singleton [États-Unis]Source :
- Nature genetics ; 2014.
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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 having genome-wide significant association; these and 6 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 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
DOI: 10.1038/ng.3043
PubMed: 25064009
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<author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John" last="Ioannidis">John. Ioannidis</name>
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<author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua" last="Bis">Joshua. Bis</name>
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<author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse</wicri:regionArea>
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<author><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel" last="Perlmutter">Joel. Perlmutter</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri</wicri:regionArea>
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<author><name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri</wicri:regionArea>
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<author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. [2] Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. [3] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [4] Department of Psychiatry, Columbia University Medical Center, New York, New York</wicri:regionArea>
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<author><name sortKey="Fiske, Brian" sort="Fiske, Brian" uniqKey="Fiske B" first="Brian" last="Fiske">Brian Fiske</name>
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<author><name sortKey="Sutherland, Margaret" sort="Sutherland, Margaret" uniqKey="Sutherland M" first="Margaret" last="Sutherland">Margaret Sutherland</name>
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<author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name>
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<country xml:lang="fr">Grèce</country>
<wicri:regionArea>1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki</wicri:regionArea>
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<author><name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard" last="Myers">Richard. Myers</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts</wicri:regionArea>
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<author><name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine" last="Clark">Lorraine. Clark</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. [2] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York</wicri:regionArea>
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<author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name>
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<country xml:lang="fr">Islande</country>
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<author><name sortKey="Hardy, John A" sort="Hardy, John A" uniqKey="Hardy J" first="John" last="Hardy">John. Hardy</name>
<affiliation wicri:level="1"><nlm:affiliation>Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London</wicri:regionArea>
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<author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen</wicri:regionArea>
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<author><name sortKey="Chen, Honglei" sort="Chen, Honglei" uniqKey="Chen H" first="Honglei" last="Chen">Honglei Chen</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina</wicri:regionArea>
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<author><name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas" last="Wood">Nicholas. Wood</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
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<author><name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name>
<affiliation wicri:level="1"><nlm:affiliation>New York State Department of Health Wadsworth Center, Albany, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>New York State Department of Health Wadsworth Center, Albany, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William. Scott</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, University of Miami School of Medicine, Miami, Florida</wicri:regionArea>
</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:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eriksson, Nicholas" sort="Eriksson, Nicholas" uniqKey="Eriksson N" first="Nicholas" last="Eriksson">Nicholas Eriksson</name>
<affiliation wicri:level="1"><nlm:affiliation>23andMe, Inc., Mountain View, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Inc., Mountain View, California</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew. Singleton</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="doi">10.1038/ng.3043</idno>
<idno type="RBID">pubmed:25064009</idno>
<idno type="pmid">25064009</idno>
<idno type="wicri:Area/PubMed/Corpus">000024</idno>
<idno type="wicri:Area/PubMed/Curation">000024</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.</title>
<author><name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike" last="Nalls">Mike. Nalls</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2].</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. [2].</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina" last="Lill">Christina. Lill</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz</wicri:regionArea>
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</author>
<author><name sortKey="Do, Chuong B" sort="Do, Chuong B" uniqKey="Do C" first="Chuong" last="Do">Chuong. Do</name>
<affiliation wicri:level="1"><nlm:affiliation>23andMe, Inc., Mountain View, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Inc., Mountain View, California</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hernandez, Dena G" sort="Hernandez, Dena G" uniqKey="Hernandez D" first="Dena" last="Hernandez">Dena. Hernandez</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2] Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2] Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Saad, Mohamad" sort="Saad, Mohamad" uniqKey="Saad M" first="Mohamad" last="Saad">Mohamad Saad</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Biostatistics, University of Washington, Seattle, Washington, USA. [2] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [3] Paul Sabatier University, Toulouse, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Department of Biostatistics, University of Washington, Seattle, Washington, USA. [2] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [3] Paul Sabatier University, Toulouse</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita" last="Destefano">Anita. Destefano</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [3] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [3] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kara, Eleanna" sort="Kara, Eleanna" uniqKey="Kara E" first="Eleanna" last="Kara">Eleanna Kara</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bras, Jose" sort="Bras, Jose" uniqKey="Bras J" first="Jose" last="Bras">Jose Bras</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
</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:affiliation>1] Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. [2] Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>1] Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. [2] Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen</wicri:regionArea>
</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:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Keller, Margaux F" sort="Keller, Margaux F" uniqKey="Keller M" first="Margaux" last="Keller">Margaux. Keller</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Arepalli, Sampath" sort="Arepalli, Sampath" uniqKey="Arepalli S" first="Sampath" last="Arepalli">Sampath Arepalli</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Letson, Christopher" sort="Letson, Christopher" uniqKey="Letson C" first="Christopher" last="Letson">Christopher Letson</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Edsall, Connor" sort="Edsall, Connor" uniqKey="Edsall C" first="Connor" last="Edsall">Connor Edsall</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</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:affiliation>deCODE Genetics, Reykjavík, Iceland.</nlm:affiliation>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE Genetics, Reykjavík</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Liu, Xinmin" sort="Liu, Xinmin" uniqKey="Liu X" first="Xinmin" last="Liu">Xinmin Liu</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pliner, Hannah" sort="Pliner, Hannah" uniqKey="Pliner H" first="Hannah" last="Pliner">Hannah Pliner</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lee, Joseph H" sort="Lee, Joseph H" uniqKey="Lee J" first="Joseph" last="Lee">Joseph. Lee</name>
<affiliation wicri:level="1"><nlm:affiliation>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cheng, Rong" sort="Cheng, Rong" uniqKey="Cheng R" first="Rong" last="Cheng">Rong Cheng</name>
<affiliation wicri:level="1"><nlm:affiliation>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M" last="Ikram">M Ikram</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [3] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [3] Department of Neurology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John" last="Ioannidis">John. Ioannidis</name>
<affiliation wicri:level="1"><nlm:affiliation>Stanford Prevention Research Center, Stanford University, Stanford, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Stanford Prevention Research Center, Stanford University, Stanford, California</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios" last="Hadjigeorgiou">Georgios. Hadjigeorgiou</name>
<affiliation wicri:level="1"><nlm:affiliation>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.</nlm:affiliation>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua" last="Bis">Joshua. Bis</name>
<affiliation wicri:level="1"><nlm:affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name>
<affiliation wicri:level="1"><nlm:affiliation>1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel" last="Perlmutter">Joel. Perlmutter</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<affiliation wicri:level="1"><nlm:affiliation>1] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. [2] Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. [3] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [4] Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. [2] Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. [3] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [4] Department of Psychiatry, Columbia University Medical Center, New York, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fiske, Brian" sort="Fiske, Brian" uniqKey="Fiske B" first="Brian" last="Fiske">Brian Fiske</name>
<affiliation wicri:level="1"><nlm:affiliation>The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Michael J. Fox Foundation for Parkinson's Research, New York, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sutherland, Margaret" sort="Sutherland, Margaret" uniqKey="Sutherland M" first="Margaret" last="Sutherland">Margaret Sutherland</name>
<affiliation wicri:level="1"><nlm:affiliation>Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland</wicri:regionArea>
</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:affiliation>1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece.</nlm:affiliation>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard" last="Myers">Richard. Myers</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine" last="Clark">Lorraine. Clark</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. [2] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. [2] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York</wicri:regionArea>
</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:affiliation>deCODE Genetics, Reykjavík, Iceland.</nlm:affiliation>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>deCODE Genetics, Reykjavík</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hardy, John A" sort="Hardy, John A" uniqKey="Hardy J" first="John" last="Hardy">John. Hardy</name>
<affiliation wicri:level="1"><nlm:affiliation>Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
<affiliation wicri:level="1"><nlm:affiliation>Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen</wicri:regionArea>
</affiliation>
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<author><name sortKey="Chen, Honglei" sort="Chen, Honglei" uniqKey="Chen H" first="Honglei" last="Chen">Honglei Chen</name>
<affiliation wicri:level="1"><nlm:affiliation>Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas" last="Wood">Nicholas. Wood</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Molecular Neuroscience, Institute of Neurology, University College London, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name>
<affiliation wicri:level="1"><nlm:affiliation>New York State Department of Health Wadsworth Center, Albany, New York, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>New York State Department of Health Wadsworth Center, Albany, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William. Scott</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, University of Miami School of Medicine, Miami, Florida</wicri:regionArea>
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</author>
<author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation wicri:level="1"><nlm:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eriksson, Nicholas" sort="Eriksson, Nicholas" uniqKey="Eriksson N" first="Nicholas" last="Eriksson">Nicholas Eriksson</name>
<affiliation wicri:level="1"><nlm:affiliation>23andMe, Inc., Mountain View, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>23andMe, Inc., Mountain View, California</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew. Singleton</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland</wicri:regionArea>
</affiliation>
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<series><title level="j">Nature genetics</title>
<idno type="e-ISSN">1546-1718</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Case-Control Studies</term>
<term>Genetic Loci</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study (methods)</term>
<term>Genotype</term>
<term>Humans</term>
<term>Parkinson Disease (genetics)</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genome-Wide Association Study</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term>
<term>Genetic Loci</term>
<term>Genetic Predisposition to Disease</term>
<term>Genotype</term>
<term>Humans</term>
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<front><div type="abstract" xml:lang="en">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 having genome-wide significant association; these and 6 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 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.</div>
</front>
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<pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">25064009</PMID>
<DateCreated><Year>2014</Year>
<Month>08</Month>
<Day>28</Day>
</DateCreated>
<DateCompleted><Year>2015</Year>
<Month>01</Month>
<Day>15</Day>
</DateCompleted>
<DateRevised><Year>2015</Year>
<Month>10</Month>
<Day>20</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-1718</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>46</Volume>
<Issue>9</Issue>
<PubDate><Year>2014</Year>
<Month>Sep</Month>
</PubDate>
</JournalIssue>
<Title>Nature genetics</Title>
<ISOAbbreviation>Nat. Genet.</ISOAbbreviation>
</Journal>
<ArticleTitle>Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.</ArticleTitle>
<Pagination><MedlinePgn>989-93</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/ng.3043</ELocationID>
<Abstract><AbstractText>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 having genome-wide significant association; these and 6 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 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nalls</LastName>
<ForeName>Mike A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2].</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Pankratz</LastName>
<ForeName>Nathan</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. [2].</Affiliation>
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<Author ValidYN="Y"><LastName>Lill</LastName>
<ForeName>Christina M</ForeName>
<Initials>CM</Initials>
<AffiliationInfo><Affiliation>1] Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. [2] Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Do</LastName>
<ForeName>Chuong B</ForeName>
<Initials>CB</Initials>
<AffiliationInfo><Affiliation>23andMe, Inc., Mountain View, California, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Hernandez</LastName>
<ForeName>Dena G</ForeName>
<Initials>DG</Initials>
<AffiliationInfo><Affiliation>1] Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. [2] Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.</Affiliation>
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<ForeName>Mohamad</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>1] Department of Biostatistics, University of Washington, Seattle, Washington, USA. [2] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [3] Paul Sabatier University, Toulouse, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>DeStefano</LastName>
<ForeName>Anita L</ForeName>
<Initials>AL</Initials>
<AffiliationInfo><Affiliation>1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. [3] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kara</LastName>
<ForeName>Eleanna</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bras</LastName>
<ForeName>Jose</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</Affiliation>
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<Author ValidYN="Y"><LastName>Sharma</LastName>
<ForeName>Manu</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>1] Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. [2] Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Schulte</LastName>
<ForeName>Claudia</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Keller</LastName>
<ForeName>Margaux F</ForeName>
<Initials>MF</Initials>
<AffiliationInfo><Affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</Affiliation>
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<ForeName>Sampath</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Letson</LastName>
<ForeName>Christopher</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Edsall</LastName>
<ForeName>Connor</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Stefansson</LastName>
<ForeName>Hreinn</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>deCODE Genetics, Reykjavík, Iceland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Xinmin</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pliner</LastName>
<ForeName>Hannah</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Lee</LastName>
<ForeName>Joseph H</ForeName>
<Initials>JH</Initials>
<AffiliationInfo><Affiliation>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Rong</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>International Parkinson's Disease Genomics Consortium (IPDGC)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>23andMe</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>GenePD</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>NeuroGenetics Research Consortium (NGRC)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Hussman Institute of Human Genomics (HIHG)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Ashkenazi Jewish Dataset Investigator</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>North American Brain Expression Consortium (NABEC)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>United Kingdom Brain Expression Consortium (UKBEC)</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Greek Parkinson's Disease Consortium</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Alzheimer Genetic Analysis Group</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Ikram</LastName>
<ForeName>M Arfan</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [2] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. [3] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ioannidis</LastName>
<ForeName>John P A</ForeName>
<Initials>JP</Initials>
<AffiliationInfo><Affiliation>Stanford Prevention Research Center, Stanford University, Stanford, California, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Hadjigeorgiou</LastName>
<ForeName>Georgios M</ForeName>
<Initials>GM</Initials>
<AffiliationInfo><Affiliation>Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.</Affiliation>
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<Author ValidYN="Y"><LastName>Bis</LastName>
<ForeName>Joshua C</ForeName>
<Initials>JC</Initials>
<AffiliationInfo><Affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Martinez</LastName>
<ForeName>Maria</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>1] INSERM, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France. [2] Paul Sabatier University, Toulouse, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Perlmutter</LastName>
<ForeName>Joel S</ForeName>
<Initials>JS</Initials>
<AffiliationInfo><Affiliation>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Goate</LastName>
<ForeName>Alison</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>1] Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. [3] Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. [4] Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Marder</LastName>
<ForeName>Karen</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>1] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA. [2] Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, New York, USA. [3] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [4] Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Fiske</LastName>
<ForeName>Brian</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Sutherland</LastName>
<ForeName>Margaret</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Neuroscience Center, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Xiromerisiou</LastName>
<ForeName>Georgia</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>1] Neuroscience Unit, Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece. [2] Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Myers</LastName>
<ForeName>Richard H</ForeName>
<Initials>RH</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Clark</LastName>
<ForeName>Lorraine N</ForeName>
<Initials>LN</Initials>
<AffiliationInfo><Affiliation>1] Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. [2] The Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Stefansson</LastName>
<ForeName>Kari</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>deCODE Genetics, Reykjavík, Iceland.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Hardy</LastName>
<ForeName>John A</ForeName>
<Initials>JA</Initials>
<AffiliationInfo><Affiliation>Reta Lila Weston Institute, University College London Institute of Neurology, Queen Square, London, UK.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Heutink</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Honglei</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Epidemiology Branch, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle, North Carolina, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Wood</LastName>
<ForeName>Nicholas W</ForeName>
<Initials>NW</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Houlden</LastName>
<ForeName>Henry</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Payami</LastName>
<ForeName>Haydeh</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>New York State Department of Health Wadsworth Center, Albany, New York, USA.</Affiliation>
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</Author>
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<ForeName>Alexis</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>1] Sorbonne Université, UPMC Université Paris 06, UM 75, INSERM U1127, Institut du Cerveau et de la Moelle, Paris, France. [2] CNRS, UMR 7225, Paris, France. [3] Pitié-Salpêtrière Hospital, Department of Genetics and Cytogenetics, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scott</LastName>
<ForeName>William K</ForeName>
<Initials>WK</Initials>
<AffiliationInfo><Affiliation>Department of Human Genetics, University of Miami School of Medicine, Miami, Florida, USA.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Gasser</LastName>
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<Investigator ValidYN="Y"><LastName>Gardner</LastName>
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<Initials>A</Initials>
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<Investigator ValidYN="Y"><LastName>van Hilten</LastName>
<ForeName>Jacobus J</ForeName>
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<Investigator ValidYN="Y"><LastName>Hollenbeck</LastName>
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<Initials>A</Initials>
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<Investigator ValidYN="Y"><LastName>Hu</LastName>
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<Investigator ValidYN="Y"><LastName>Huang</LastName>
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<Investigator ValidYN="Y"><LastName>Wurster</LastName>
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<Investigator ValidYN="Y"><LastName>Mätzler</LastName>
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<Investigator ValidYN="Y"><LastName>Hudson</LastName>
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<Investigator ValidYN="Y"><LastName>Hunt</LastName>
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<Investigator ValidYN="Y"><LastName>Huttenlocher</LastName>
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<Investigator ValidYN="Y"><LastName>Illig</LastName>
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<Investigator ValidYN="Y"><LastName>Jónsson</LastName>
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<Investigator ValidYN="Y"><LastName>Morris</LastName>
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<Investigator ValidYN="Y"><LastName>Morrison</LastName>
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<Investigator ValidYN="Y"><LastName>Mudanohwo</LastName>
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<Investigator ValidYN="Y"><LastName>O'Sullivan</LastName>
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<Investigator ValidYN="Y"><LastName>Pearson</LastName>
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<Investigator ValidYN="Y"><LastName>Perlmutter</LastName>
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<Investigator ValidYN="Y"><LastName>Pétursson</LastName>
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<Investigator ValidYN="Y"><LastName>Pollak</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Post</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Potter</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Ravina</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Revesz</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Riess</LastName>
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<Initials>O</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Rivadeneira</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Rizzu</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Ryten</LastName>
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<Investigator ValidYN="Y"><LastName>Sawcer</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Schapira</LastName>
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<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Scheffer</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Shaw</LastName>
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<Initials>K</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Shoulson</LastName>
<ForeName>Ira</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Sidransky</LastName>
<ForeName>Ellen</ForeName>
<Initials>E</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Smith</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Spencer</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Stefánsson</LastName>
<ForeName>Hreinn</ForeName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Bettella</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Stockton</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Strange</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Talbot</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Tanner</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Tashakkori-Ghanbaria</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Tison</LastName>
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</Investigator>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Traynor</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Uitterlinden</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Velseboer</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Vidailhet</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Walker</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>van de Warrenburg</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Wickremaratchi</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Williams</LastName>
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</Investigator>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Winder-Rhodes</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Stefánsson</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Martinez</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Wood</LastName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Hardy</LastName>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Singleton</LastName>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Morehouse</LastName>
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</Investigator>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Mendis</LastName>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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</Investigator>
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<Initials>I</Initials>
</Investigator>
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<Initials>A</Initials>
</Investigator>
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</Investigator>
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</Investigator>
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<Initials>B</Initials>
</Investigator>
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</Investigator>
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<Initials>D</Initials>
</Investigator>
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<Initials>A</Initials>
</Investigator>
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</Investigator>
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<Initials>P</Initials>
</Investigator>
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<Initials>JW</Initials>
</Investigator>
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