Chang, D; Nalls, MA; Hallgrímsdóttir, IB; Hunkapiller, J; van der Brug, M; Cai, F; Kerchner, GA; ... Graham, RR; + view all Chang, D; Nalls, MA; Hallgrímsdóttir, IB; Hunkapiller, J; van der Brug, M; Cai, F; Kerchner, GA; Ayalon, G; Bingol, B; Sheng, M; Hinds, D; Behrens, TW; Singleton, AB; Bhangale, TR; Graham, RR; - view fewer (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nature Genetics , 49 (10) pp. 1511-1516. 10.1038/ng.3955.

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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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