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A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
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A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
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Journal Article
A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
2017
Overview
Robert Graham and colleagues carried out a GWAS meta-analysis for Parkinson's disease (PD) and report 17 new risk loci. Their analyses support a key role for autophagy and lysosomal biology in PD risk.
Common variant genome-wide association studies (GWASs) have, to date, identified >24 risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS comparing 6,476 PD cases with 302,042 controls, followed by a meta-analysis with a recent study of over 13,000 PD cases and 95,000 controls at 9,830 overlapping variants. We then tested 35 loci (
P
< 1 × 10
−6
) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (
P
< 5 × 10
−8
) in a joint analysis of 26,035 cases and 403,190 controls. We used a neurocentric strategy to assign candidate risk genes to the loci. We identified protein-altering or
cis
–expression quantitative trait locus (
cis
-eQTL) variants in linkage disequilibrium with the index variant in 29 of the 41 PD loci. These results indicate a key role for autophagy and lysosomal biology in PD risk, and suggest potential new drug targets for PD.
Publisher
Springer New York,Nature Publishing Group
Subject
/ Acids
/ Animal Genetics and Genomics
/ Antiparkinson Agents - pharmacology
/ Biology
/ Genes
/ Genetic Predisposition to Disease
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Insects
/ letter
/ Methods
/ Ontology
/ Parkinson Disease - drug therapy
/ Parkinson Disease - epidemiology
/ Parkinson Disease - genetics
/ Proteins
/ Risk
/ Studies
