A Meta-Analysis of Genome-Wide Association Studies Identifies 17 New Parkinson's Disease Risk Loci

Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Antiparkinson Agents / pharmacology
  • Autophagy / genetics
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Linkage Disequilibrium
  • Lysosomes / physiology
  • Molecular Targeted Therapy
  • Parkinson Disease / drug therapy
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Risk
  • Transcription Factors

Substances

  • Antiparkinson Agents
  • Transcription Factors