Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

被引：435

作者：

Lill, Christina M. ^{[1
,2
,3
,4
]}

Roehr, Johannes T. ^{[1
,5
]}

McQueen, Matthew B. ^{[6
]}

Kavvoura, Fotini K. ^{[7
,8
,9
]}

Bagade, Sachin ^{[2
]}

Schjeide, Brit-Maren M. ^{[1
]}

Schjeide, Leif M. ^{[1
]}

Meissner, Esther ^{[1
]}

Zauft, Ute ^{[1
]}

Allen, Nicole C. ^{[2
]}

Liu, Tian ^{[1
,10
]}

Schilling, Marcel ^{[1
,5
]}

Anderson, Kari J. ^{[11
]}

Beecham, Gary ^{[12
]}

Berg, Daniela ^{[13
,14
]}

Biernacka, Joanna M. ^{[11
]}

Brice, Alexis ^{[15
,16
,17
,18
]}

DeStefano, Anita L. ^{[19
,20
]}

Do, Chuong B. ^{[21
]}

Eriksson, Nicholas ^{[21
]}

Factor, Stewart A. ^{[22
]}

Farrer, Matthew J. ^{[23
]}

Foroud, Tatiana ^{[24
]}

Gasser, Thomas ^{[13
,14
]}

Hamza, Taye ^{[25
]}

Hardy, John A. ^{[26
]}

Heutink, Peter ^{[27
]}

Hill-Burns, Erin M. ^{[25
]}

Klein, Christine ^{[28
]}

Latourelle, Jeanne C. ^{[19
]}

Maraganore, Demetrius M. ^{[29
]}

Martin, Eden R. ^{[12
]}

Martinez, Maria ^{[30
,31
]}

Myers, Richard H. ^{[19
]}

Nalls, Michael A. ^{[32
]}

Pankratz, Nathan ^{[24
]}

Payami, Haydeh ^{[25
]}

Satake, Wataru ^{[33
]}

Scott, William K. ^{[12
]}

Sharma, Manu ^{[13
,14
]}

Singleton, Andrew B. ^{[32
]}

Stefansson, Kari ^{[35
]}

Toda, Tatsushi ^{[33
]}

Tung, Joyce Y. ^{[21
]}

Vance, Jeffery ^{[12
]}

Wood, Nick W. ^{[26
,34
]}

Zabetian, Cyrus P. ^{[36
,37
]}

Young, Peter ^{[4
]}

Tanzi, Rudolph E. ^{[2
]}

Khoury, Muin J. ^{[38
]}

机构：

[1] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany

[2] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA

[3] Johannes Gutenberg Univ Mainz, Dept Neurol, Med Ctr, Mainz, Germany

[4] Univ Hosp, Dept Neurol, Munster, Germany

[5] Free Univ Berlin, Dept Math & Comp Sci, Berlin, Germany

[6] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[7] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[8] Royal Berkshire Hosp, Ctr Diabet & Endocrinol, Reading RG1 5AN, Berks, England

[9] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England

[10] Max Planck Inst Human Dev, Berlin, Germany

[11] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[12] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA

[13] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany

[14] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany

[15] INSERM, UMR S975, Paris, France

[16] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France

[17] CNRS, UMR 7225, Paris, France

[18] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France

[19] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[20] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[21] 23andMe, Mountain View, CA USA

[22] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

[23] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[24] Indiana Univ Sch Med, Indianapolis, IN USA

[25] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA

[26] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England

[27] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands

[28] Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, Lubeck, Germany

[29] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA

[30] Fac Med Toulouse, INSERM, UMR 1043, CPTP, F-31073 Toulouse, France

[31] Univ Toulouse 3, F-31062 Toulouse, France

[32] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[33] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan

[34] UCL, UCL Genet Inst, London, England

[35] deCODE Genet, Reykjavik, Iceland

[36] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA

[37] Univ Washington, Dept Neurol, Seattle, WA USA

[38] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA

[39] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece

[40] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA

[41] Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA

[42] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA

[43] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA

来源：

PLOS GENETICS | 2012年 / 8卷 / 03期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; MUTATIONS; VARIANTS; SUSCEPTIBILITY; REGION; VPS35; LOCI; SNCA;

D O I：

10.1371/journal.pgen.1002548

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ~27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P>5×10-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10-8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

引用

页数：10

共 34 条

[1]

Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database [J].

Allen, Nicole C. ;

Bagade, Sachin ;

McQueen, Matthew B. ;

Ioannidis, John P. A. ;

Kavvoura, Fotini K. ;

Khoury, Muin J. ;

Tanzi, Rudolph E. ;

Bertram, Lars .

NATURE GENETICS, 2008, 40 (07) :827-834

[2]

Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database [J].

Bertram, Lars ;

McQueen, Matthew B. ;

Mullin, Kristina ;

Blacker, Deborah ;

Tanzi, Rudolph E. .

NATURE GENETICS, 2007, 39 (01) :17-23

[3]

Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease [J].

Chartier-Harlin, Marie-Christine ;

Dachsel, Justus C. ;

Vilarino-Gueell, Carles ;

Lincoln, Sarah J. ;

Lepretre, Frederic ;

Hulihan, Mary M. ;

Kachergus, Jennifer ;

Milnerwood, Austen J. ;

Tapia, Lucia ;

Song, Mee-Sook ;

Le Rhun, Emilie ;

Mutez, Eugenie ;

Larvor, Lydie ;

Duflot, Aurelie ;

Vanbesien-Mailliot, Christel ;

Kreisler, Alexandre ;

Ross, Owen A. ;

Nishioka, Kenya ;

Soto-Ortolaza, Alexandra I. ;

Cobb, Stephanie A. ;

Melrose, Heather L. ;

Behrouz, Bahareh ;

Keeling, Brett H. ;

Bacon, Justin A. ;

Hentati, Emna ;

Williams, Lindsey ;

Yanagiya, Akiko ;

Sonenberg, Nahum ;

Lockhart, Paul J. ;

Zubair, Abba C. ;

Uitti, Ryan J. ;

Aasly, Jan O. ;

Krygowska-Wajs, Anna ;

Opala, Grzegorz ;

Wszolek, Zbigniew K. ;

Frigerio, Roberta ;

Maraganore, Demetrius M. ;

Gosal, David ;

Lynch, Tim ;

Hutchinson, Michael ;

Bentivoglio, Anna Rita ;

Valente, Enza Maria ;

Nicholso, William C. ;

Pankratz, Nathan ;

Foroud, Tatiana ;

Gibson, Rachel A. ;

Hentati, Faycal ;

Dickson, Dennis W. ;

Destee, Alain ;

Farrer, Matthew J. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 89 (03) :398-406

[4]

Epidemiology of Parkinson's disease [J].

de Lau, Lonneke M. L. ;

Breteler, Monique M. B. .

LANCET NEUROLOGY, 2006, 5 (06) :525-535

[5]

METAANALYSIS IN CLINICAL-TRIALS [J].

DERSIMONIAN, R ;

LAIRD, N .

CONTROLLED CLINICAL TRIALS, 1986, 7 (03) :177-188

[6]

Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease [J].

Do, Chuong B. ;

Tung, Joyce Y. ;

Dorfman, Elizabeth ;

Kiefer, Amy K. ;

Drabant, Emily M. ;

Francke, Uta ;

Mountain, Joanna L. ;

Goldman, Samuel M. ;

Tanner, Caroline M. ;

Langston, J. William ;

Wojcicki, Anne ;

Eriksson, Nicholas .

PLOS GENETICS, 2011, 7 (06)

[7]

Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease [J].

Edwards, Todd L. ;

Scott, William K. ;

Almonte, Cherylyn ;

Burt, Amber ;

Powell, Eric H. ;

Beecham, Gary W. ;

Wang, Liyong ;

Zuchner, Stephan ;

Konidari, Ioanna ;

Wang, Gaofeng ;

Singer, Carlos ;

Nahab, Fatta ;

Scott, Burton ;

Stajich, Jeffrey M. ;

Pericak-Vance, Margaret ;

Haines, Jonathan ;

Vance, Jeffery M. ;

Martin, Eden R. .

ANNALS OF HUMAN GENETICS, 2010, 74 :97-109

[8]

Meta-Analysis in Genome-Wide Association Datasets: Strategies and Application in Parkinson Disease [J].

Evangelou, Evangelos ;

Maraganore, Demetrius M. ;

Ioannidis, John P. A. .

PLOS ONE, 2007, 2 (02)

[9]

Genome-wide genotyping in Parkinson's disease and neurologically normal controls:: first stage analysis and public release of data [J].

Fung, Hon-Chung ;

Scholz, Sonja ;

Matarin, Mar ;

Simon-Sanchez, Javier ;

Hernandez, Dena ;

Britton, Angela ;

Gibbs, J. Raphael ;

Langefeld, Carl ;

Stiegert, Matt L. ;

Schymick, Jennifer ;

Okun, Michael S. ;

Mandel, Ronald J. ;

Fernandez, Hubert H. ;

Foote, Kelly D. ;

Rodriguez, Ramon L. ;

Peckham, Elizabeth ;

De Vrieze, Fabienne Wavrant ;

Gwinn-Hardy, Katrina ;

Hardy, John A. ;

Singleton, Andrew .

LANCET NEUROLOGY, 2006, 5 (11) :911-916

[10]

Tau and α-synuclein in susceptibility to, and dementia in, Parkinson's disease [J].

Goris, An ;

Williams-Gray, Caroline H. ;

Clark, Graeme R. ;

Foltynie, Thomas ;

Lewis, Simon J. G. ;

Brown, Joanne ;

Ban, Maria ;

Spillantini, Maria G. ;

Compston, Alastair ;

Burn, David J. ;

Chinnery, Patrick F. ;

Barker, Roger A. ;

Sawcer, Stephen J. .

ANNALS OF NEUROLOGY, 2007, 62 (02) :145-153

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