Novel Parkinson’s Disease Genetic Risk Factors Within and Across European Populations

We conducted a meta-analysis of Parkinson’s disease genome-wide association study summary statistics, stratified by source (clinically-recruited case-control cohorts versus population biobanks) and by general European versus European isolate ancestries. This study included 63,555 cases, 17,700 proxy cases with a family history of Parkinson’s disease, and 1,746,386 controls, making it the largest investigation of Parkinson’s disease genetic risk to date. The final combined cross-European meta-analysis identified 134 risk loci (59 novel), with a total of 157 independent signals, significantly expanding our understanding of Parkinson’s disease risk. Multi-omic data integration revealed that expression of the nominated risk genes are highly enriched in brain tissues, particularly in neuronal and astrocyte cell types. Additionally, we prioritized 33 high-confidence genes across these 134 loci for future follow-up studies.