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

作者：Chang, Diana; Nalls, Mike A.; Hallgrimsdottir, Ingileif B.; Hunkapiller, Julie; van der Brug, Marcel; Cai, Fang; Kerchner, Geoffrey A.; Ayalon, Gai; Bingol, Baris; Sheng, Morgan; Hinds, David; Behrens, Timothy W.; Singleton, Andrew B.; Bhangale, Tushar R.; Graham, Robert R.^*

来源：Nature Genetics, 2017, 49(10): 1511-+.

DOI：10.1038/ng.3955

• IMPUTATION
• GENETICS
• DATABASE
• VARIANTS
• TRANSCRIPTOME
• HERITABILITY
• ALZHEIMERS
• CATHEPSINS
• IMMUNITY
• PROGRESS

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.

• 出版日期2017-10