biostudies-literatureChang DIntramural NIH HHSParkinson's UK1511-1516https://www.ebi.ac.uk/biostudies/studies/S-EPMC5812477biostudies-literatureUnknown49(10)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.Nature geneticsA meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.PMC5812477G-1307Z99 AG999999International Parkinson's Disease Genomics ConsortiumAyalon GSingleton ABHunkapiller JHinds DCai FBehrens TWBingol B23andMe Research TeamKerchner GASheng MHallgrimsdottir IBChang DBhangale TRGraham RRvan der Brug MNalls MAfalseA meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.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.2017-01-01T00:00:00Z2017 Oct2021-02-19T23:22:28Z2019-03-26T23:03:00ZS-EPMC58124772889205910.1038/ng.3955