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



Quinn, JP ORCID: 0000-0003-3551-7803, Billingsley, Kimberley, Chang, D, Nalls, MA, Hallgrímsdóttir, IB, Hunkapiller, J, van der Brug, M, Cai, F, International Parkinson's Disease Genomics Consortium, , 23andMe Research Team,
et al (show 9 more authors) (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nature Genetics, 49 (10). 1511 - 1516.

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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.

Item Type: Article
Uncontrolled Keywords: Genome-wide association studies, Parkinson's disease
Depositing User: Symplectic Admin
Date Deposited: 04 Jun 2018 09:46
Last Modified: 15 Oct 2021 03:10
DOI: 10.1038/ng.3955
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3022135