A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

D Chang, MA Nalls, IB Hallgrímsdóttir, J Hunkapiller… - Nature …, 2017 - nature.com
D Chang, MA Nalls, IB Hallgrímsdóttir, J Hunkapiller, M Van Der Brug, F Cai…
Nature genetics, 2017nature.com
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 …
Abstract
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.
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