Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database

Christina M. Lill; Johannes T. Roehr; Matthew B. McQueen; Fotini K. Kavvoura; Sachin Bagade; Brit Maren M. Schjeide; Leif M. Schjeide; Esther Meissner; Ute Zauft; Nicole C. Allen; Tian Liu; Marcel Schilling; Kari J. Anderson; Gary Beecham; Daniela Berg; Joanna M. Biernacka; Alexis Brice; Anita L. DeStefano; Chuong B. Do; Nicholas Eriksson; Stewart A. Factor; Matthew J. Farrer; Tatiana Foroud; Thomas Gasser; Taye Hamza; John A. Hardy; Peter Heutink; Erin M. Hill-Burns; Christine Klein; Jeanne C. Latourelle; Demetrius M. Maraganore; Eden R. Martin; Maria Martinez; Richard H. Myers; Michael A. Nalls; Nathan Pankratz; Haydeh Payami; Wataru Satake; William K. Scott; Manu Sharma; Andrew B. Singleton; Kari Stefansson; Tatsushi Toda; Joyce Y. Tung; Jeffery Vance; Nick W. Wood; Cyrus P. Zabetian; Peter Young; Rudolph E. Tanzi; Muin J. Khoury; Frauke Zipp; Hans Lehrach; John P.A. Ioannidis; Lars Bertram

doi:10.1371/journal.pgen.1002548

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database

Christina M. Lill, Johannes T. Roehr, Matthew B. McQueen, Fotini K. Kavvoura, Sachin Bagade, Brit Maren M. Schjeide, Leif M. Schjeide, Esther Meissner, Ute Zauft, Nicole C. Allen, Tian Liu, Marcel Schilling, Kari J. Anderson, Gary Beecham, Daniela Berg, Joanna M. Biernacka, Alexis Brice, Anita L. DeStefano, Chuong B. Do, Nicholas ErikssonStewart A. Factor, Matthew J. Farrer, Tatiana Foroud, Thomas Gasser, Taye Hamza, John A. Hardy, Peter Heutink, Erin M. Hill-Burns, Christine Klein, Jeanne C. Latourelle, Demetrius M. Maraganore, Eden R. Martin, Maria Martinez, Richard H. Myers, Michael A. Nalls, Nathan Pankratz, Haydeh Payami, Wataru Satake, William K. Scott, Manu Sharma, Andrew B. Singleton, Kari Stefansson, Tatsushi Toda, Joyce Y. Tung, Jeffery Vance, Nick W. Wood, Cyrus P. Zabetian, Peter Young, Rudolph E. Tanzi, Muin J. Khoury, Frauke Zipp, Hans Lehrach, John P.A. Ioannidis, Lars Bertram

Health Sciences Research

Research output: Contribution to journal › Article › peer-review

385 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e1002548
Journal	PLoS genetics
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1002548
State	Published - Mar 2012

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Lill, C. M., Roehr, J. T., McQueen, M. B., Kavvoura, F. K., Bagade, S., Schjeide, B. M. M., Schjeide, L. M., Meissner, E., Zauft, U., Allen, N. C., Liu, T., Schilling, M., Anderson, K. J., Beecham, G., Berg, D., Biernacka, J. M., Brice, A., DeStefano, A. L., Do, C. B., ... Bertram, L. (2012). Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database. PLoS genetics, 8(3), [e1002548]. https://doi.org/10.1371/journal.pgen.1002548

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics : The PDgene database. / Lill, Christina M.; Roehr, Johannes T.; McQueen, Matthew B.; Kavvoura, Fotini K.; Bagade, Sachin; Schjeide, Brit Maren M.; Schjeide, Leif M.; Meissner, Esther; Zauft, Ute; Allen, Nicole C.; Liu, Tian; Schilling, Marcel; Anderson, Kari J.; Beecham, Gary; Berg, Daniela; Biernacka, Joanna M.; Brice, Alexis; DeStefano, Anita L.; Do, Chuong B.; Eriksson, Nicholas; Factor, Stewart A.; Farrer, Matthew J.; Foroud, Tatiana; Gasser, Thomas; Hamza, Taye; Hardy, John A.; Heutink, Peter; Hill-Burns, Erin M.; Klein, Christine; Latourelle, Jeanne C.; Maraganore, Demetrius M.; Martin, Eden R.; Martinez, Maria; Myers, Richard H.; Nalls, Michael A.; Pankratz, Nathan; Payami, Haydeh; Satake, Wataru; Scott, William K.; Sharma, Manu; Singleton, Andrew B.; Stefansson, Kari; Toda, Tatsushi; Tung, Joyce Y.; Vance, Jeffery; Wood, Nick W.; Zabetian, Cyrus P.; Young, Peter; Tanzi, Rudolph E.; Khoury, Muin J.; Zipp, Frauke; Lehrach, Hans; Ioannidis, John P.A.; Bertram, Lars.

In: PLoS genetics, Vol. 8, No. 3, e1002548, 03.2012.

Research output: Contribution to journal › Article › peer-review

Lill, CM, Roehr, JT, McQueen, MB, Kavvoura, FK, Bagade, S, Schjeide, BMM, Schjeide, LM, Meissner, E, Zauft, U, Allen, NC, Liu, T, Schilling, M, Anderson, KJ, Beecham, G, Berg, D, Biernacka, JM, Brice, A, DeStefano, AL, Do, CB, Eriksson, N, Factor, SA, Farrer, MJ, Foroud, T, Gasser, T, Hamza, T, Hardy, JA, Heutink, P, Hill-Burns, EM, Klein, C, Latourelle, JC, Maraganore, DM, Martin, ER, Martinez, M, Myers, RH, Nalls, MA, Pankratz, N, Payami, H, Satake, W, Scott, WK, Sharma, M, Singleton, AB, Stefansson, K, Toda, T, Tung, JY, Vance, J, Wood, NW, Zabetian, CP, Young, P, Tanzi, RE, Khoury, MJ, Zipp, F, Lehrach, H, Ioannidis, JPA & Bertram, L 2012, 'Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database', PLoS genetics, vol. 8, no. 3, e1002548. https://doi.org/10.1371/journal.pgen.1002548

Lill, Christina M. ; Roehr, Johannes T. ; McQueen, Matthew B. ; Kavvoura, Fotini K. ; Bagade, Sachin ; Schjeide, Brit Maren M. ; Schjeide, Leif M. ; Meissner, Esther ; Zauft, Ute ; Allen, Nicole C. ; Liu, Tian ; Schilling, Marcel ; Anderson, Kari J. ; Beecham, Gary ; Berg, Daniela ; Biernacka, Joanna M. ; Brice, Alexis ; DeStefano, Anita L. ; Do, Chuong B. ; Eriksson, Nicholas ; Factor, Stewart A. ; Farrer, Matthew J. ; Foroud, Tatiana ; Gasser, Thomas ; Hamza, Taye ; Hardy, John A. ; Heutink, Peter ; Hill-Burns, Erin M. ; Klein, Christine ; Latourelle, Jeanne C. ; Maraganore, Demetrius M. ; Martin, Eden R. ; Martinez, Maria ; Myers, Richard H. ; Nalls, Michael A. ; Pankratz, Nathan ; Payami, Haydeh ; Satake, Wataru ; Scott, William K. ; Sharma, Manu ; Singleton, Andrew B. ; Stefansson, Kari ; Toda, Tatsushi ; Tung, Joyce Y. ; Vance, Jeffery ; Wood, Nick W. ; Zabetian, Cyrus P. ; Young, Peter ; Tanzi, Rudolph E. ; Khoury, Muin J. ; Zipp, Frauke ; Lehrach, Hans ; Ioannidis, John P.A. ; Bertram, Lars. / Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics : The PDgene database. In: PLoS genetics. 2012 ; Vol. 8, No. 3.

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title = "Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database",

abstract = "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.",

author = "Lill, {Christina M.} and Roehr, {Johannes T.} and McQueen, {Matthew B.} and Kavvoura, {Fotini K.} and Sachin Bagade and Schjeide, {Brit Maren M.} and Schjeide, {Leif M.} and Esther Meissner and Ute Zauft and Allen, {Nicole C.} and Tian Liu and Marcel Schilling and Anderson, {Kari J.} and Gary Beecham and Daniela Berg and Biernacka, {Joanna M.} and Alexis Brice and DeStefano, {Anita L.} and Do, {Chuong B.} and Nicholas Eriksson and Factor, {Stewart A.} and Farrer, {Matthew J.} and Tatiana Foroud and Thomas Gasser and Taye Hamza and Hardy, {John A.} and Peter Heutink and Hill-Burns, {Erin M.} and Christine Klein and Latourelle, {Jeanne C.} and Maraganore, {Demetrius M.} and Martin, {Eden R.} and Maria Martinez and Myers, {Richard H.} and Nalls, {Michael A.} and Nathan Pankratz and Haydeh Payami and Wataru Satake and Scott, {William K.} and Manu Sharma and Singleton, {Andrew B.} and Kari Stefansson and Tatsushi Toda and Tung, {Joyce Y.} and Jeffery Vance and Wood, {Nick W.} and Zabetian, {Cyrus P.} and Peter Young and Tanzi, {Rudolph E.} and Khoury, {Muin J.} and Frauke Zipp and Hans Lehrach and Ioannidis, {John P.A.} and Lars Bertram",

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AU - Lill, Christina M.

AU - Roehr, Johannes T.

AU - McQueen, Matthew B.

AU - Kavvoura, Fotini K.

AU - Bagade, Sachin

AU - Schjeide, Brit Maren M.

AU - Schjeide, Leif M.

AU - Meissner, Esther

AU - Zauft, Ute

AU - Allen, Nicole C.

AU - Liu, Tian

AU - Schilling, Marcel

AU - Anderson, Kari J.

AU - Beecham, Gary

AU - Berg, Daniela

AU - Biernacka, Joanna M.

AU - Brice, Alexis

AU - DeStefano, Anita L.

AU - Do, Chuong B.

AU - Eriksson, Nicholas

AU - Factor, Stewart A.

AU - Farrer, Matthew J.

AU - Foroud, Tatiana

AU - Gasser, Thomas

AU - Hamza, Taye

AU - Hardy, John A.

AU - Heutink, Peter

AU - Hill-Burns, Erin M.

AU - Klein, Christine

AU - Latourelle, Jeanne C.

AU - Maraganore, Demetrius M.

AU - Martin, Eden R.

AU - Martinez, Maria

AU - Myers, Richard H.

AU - Nalls, Michael A.

AU - Pankratz, Nathan

AU - Payami, Haydeh

AU - Satake, Wataru

AU - Scott, William K.

AU - Sharma, Manu

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AU - Stefansson, Kari

AU - Toda, Tatsushi

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AU - Vance, Jeffery

AU - Wood, Nick W.

AU - Zabetian, Cyrus P.

AU - Young, Peter

AU - Tanzi, Rudolph E.

AU - Khoury, Muin J.

AU - Zipp, Frauke

AU - Lehrach, Hans

AU - Ioannidis, John P.A.

AU - Bertram, Lars

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