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

Nalls, M.A. and Pankratz, N. and Lill, C.M. and et al, . (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature Genetics, 46. pp. 989-993.

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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

Item Type: Article
Uncontrolled Keywords: Parkinson’s disease, locus, DNA methylation, NeuroX, Genetic risk
Author Affiliation: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA
Subjects: Crop Improvement > Genetics
Divisions: General
Depositing User: Ms Ishrath Durafsha
Date Deposited: 04 Feb 2015 05:20
Last Modified: 04 Feb 2015 05:20
Official URL: http://dx.doi.org/10.1038/ng.3043
URI: http://eprints.icrisat.ac.in/id/eprint/13551

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