Objective: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average $ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner.

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, all studies have been performed in just one population at the time. Here we performed the first large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases, and 2,458,063 controls including individuals of European, East Asian, Latin American, and African ancestry. In a single joint meta-analysis, we identified 78 independent genome-wide significant loci including 12 potentially novel loci (MTF2, RP11-360P21.2, ADD1, SYBU, IRS2, USP8:RP11-562A8.5, PIGL, FASN, MYLK2, AJ006998.2, Y_RNA, PPP6R2) and finemapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 23 genes near these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

No abstract