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 Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls.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 | |
| State | Published - Mar 2012 |
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ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Ecology, Evolution, Behavior and Systematics
- Cancer Research
- Genetics(clinical)
Cite this
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
}
TY - JOUR
T1 - Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics
T2 - The PDgene database
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
AU - Singleton, Andrew B.
AU - Stefansson, Kari
AU - Toda, Tatsushi
AU - Tung, Joyce Y.
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
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1002548
DO - 10.1371/journal.pgen.1002548
M3 - Article
C2 - 22438815
AN - SCOPUS:84859339977
VL - 8
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 3
M1 - e1002548
ER -