Journal
NATURE GENETICS
Volume 49, Issue 10, Pages 1511-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.3955
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- Parkinson's UK [G-1307] Funding Source: researchfish
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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 x 10(-6)) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (P < 5 x 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.
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