| Literature DB >> 28892059 |
Diana Chang1, Mike A Nalls2,3, Ingileif B Hallgrímsdóttir4, Julie Hunkapiller1, Marcel van der Brug1, Fang Cai1, Geoffrey A Kerchner1, Gai Ayalon1, Baris Bingol1, Morgan Sheng1, David Hinds4, Timothy W Behrens1, Andrew B Singleton2, Tushar R Bhangale1, Robert R Graham1.
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.Entities:
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Year: 2017 PMID： 28892059 PMCID： PMC5812477 DOI： 10.1038/ng.3955
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330