TY - JOUR
T1 - Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
AU - Greek Parkinson’s Disease Consortium
AU - Alzheimer Genetic Analysis Group
AU - International Parkinson’s Disease Genomics Consortium (IPDGC)
AU - Parkinson’s Study Group (PSG) Parkinson’s Research: The Organized GENetics Initiative (PROGENI)
AU - 23andMe
AU - GenePD
AU - NeuroGenetics Research Consortium (NGRC)
AU - Hussman Institute of Human Genomics (HIHG)
AU - The Ashkenazi Jewish Dataset Investigator
AU - Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)
AU - North American Brain Expression Consortium (NABEC)
AU - United Kingdom Brain Expression Consortium (UKBEC)
AU - Nalls, Mike A.
AU - Pankratz, Nathan
AU - Lill, Christina M.
AU - Do, Chuong B.
AU - Hernandez, Dena G.
AU - Saad, Mohamad
AU - Destefano, Anita L.
AU - Kara, Eleanna
AU - Bras, Jose
AU - Sharma, Manu
AU - Schulte, Claudia
AU - Keller, Margaux F.
AU - Arepalli, Sampath
AU - Letson, Christopher
AU - Edsall, Connor
AU - Stefansson, Hreinn
AU - Liu, Xinmin
AU - Pliner, Hannah
AU - Lee, Joseph H.
AU - Cheng, Rong
AU - Ikram, M. Arfan
AU - Ioannidis, John P.A.
AU - Hadjigeorgiou, Georgios M.
AU - Bis, Joshua C.
AU - Martinez, Maria
AU - Perlmutter, Joel S.
AU - Goate, Alison
AU - Marder, Karen
AU - Fiske, Brian
AU - Sutherland, Margaret
AU - Xiromerisiou, Georgia
AU - Myers, Richard H.
AU - Clark, Lorraine N.
AU - Stefansson, Kari
AU - Hardy, John A.
AU - Heutink, Peter
AU - Chen, Honglei
AU - Wood, Nicholas W.
AU - Houlden, Henry
AU - Payami, Haydeh
AU - Brice, Alexis
AU - Scott, William K.
AU - Gasser, Thomas
AU - Bertram, Lars
AU - Eriksson, Nicholas
AU - Foroud, Tatiana
AU - Singleton, Andrew B.
AU - Plagnol, Vincent
AU - Sheerin, Una Marie
AU - Simón-Sánchez, Javier
N1 - Publisher Copyright:
© 2014 Nature America, Inc. All rights reserved.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84939599004
U2 - 10.1038/ng.3043
DO - 10.1038/ng.3043
M3 - Article
C2 - 25064009
AN - SCOPUS:84939599004
SN - 1061-4036
VL - 46
SP - 989
EP - 993
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -