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
N1 - Funding Information:
CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE.
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.
UR - http://www.scopus.com/inward/record.url?scp=84859339977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859339977&partnerID=8YFLogxK
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 -