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

By Diana Chang, M. Nalls, Ingileif B. Hallgrímsdóttir, J. Hunkapiller, M. P. van der Brug, Fang Cai, Geoffrey A. Kerchner, Gai Ayalon, Baris Bingol, Morgan Sheng and 5 more. Nature Genetics, 2017

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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 × 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.

Subfields: Epidemiology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/3c840aebd0b00ee8c5c5a67eeaabc8c1ec153bf9

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