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Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Title: Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Authors: Nalls, MA
Pankratz, N
Lill, CM
Do, CB
Hernandez, DG
Saad, M
DeStefano, AL
Kara, E
Bras, J
Sharma, M
Schulte, C
Keller, MF
Arepalli, S
Letson, C
Edsall, C
Stefansson, H
Liu, X
Pliner, H
Lee, JH
Cheng, R
Ikram, MA
Ioannidis, JPA
Hadjigeorgiou, GM
Bis, JC
Martinez, M
Perlmutter, JS
Goate, A
Marder, K
Fiske, B
Sutherland, M
Xiromerisiou, G
Myers, RH
Clark, LN
Stefansson, K
Hardy, JA
Heutink, P
Chen, H
Wood, NW
Houlden, H
Payami, H
Brice, A
Scott, WK
Gasser, T
Bertram, L
Eriksson, N
Foroud, T
Singleton, AB
Item Type: Journal Article
Abstract: 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.
Issue Date: 1-Sep-2014
Date of Acceptance: 30-Jun-2014
URI: http://hdl.handle.net/10044/1/30049
DOI: 10.1038/ng.3043
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 989
End Page: 993
Journal / Book Title: Nature Genetics
Volume: 46
Issue: 9
Copyright Statement: © 2014, Rights Managed by Nature Publishing Group
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Case-Control Studies
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Parkinson Disease
Polymorphism, Single Nucleotide
Risk Factors
International Parkinson's Disease Genomics Consortium (IPDGC)
Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)
NeuroGenetics Research Consortium (NGRC)
Hussman Institute of Human Genomics (HIHG)
Ashkenazi Jewish Dataset Investigator
Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)
North American Brain Expression Consortium (NABEC)
United Kingdom Brain Expression Consortium (UKBEC)
Greek Parkinson's Disease Consortium
Alzheimer Genetic Analysis Group
Parkinson Disease
Genetic Predisposition to Disease
Risk Factors
Case-Control Studies
Polymorphism, Single Nucleotide
Genome-Wide Association Study
Genetic Loci
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Appears in Collections:Faculty of Medicine
School of Public Health
Department of Brain Sciences