Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Author(s)
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.
Date Issued
2014-09-01
Date Acceptance
2014-06-30
Citation
Nature Genetics, 2014, 46 (9), pp.989-993
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
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
IMPUTATION
VARIANTS
POPULATION
PREDICTION
REGION
GENES
HEART
SIZE
Publication Status
Published