ArticlemedRxiv : the preprint server for health sciences2026
Shared and Sex-Specific Genetic Risk for Parkinson's Disease Risk Across European Populations.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Parkinson's disease (PD) affects females and males differently, with differences in prevalence, clinical phenotypes, and therapeutic response, suggesting that biological sex may influence the underlying molecular mechanisms of PD. The extent to which genetic factors may contribute to these differences remains largely unknown. Objective: To investigate sex-specific autosomal genetic factors associated with PD risk. Methods: We performed a sex-stratified autosomal GWAS meta-analysis leveraging data from the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium, the UK Biobank, and the Fox Insight Genetics Study, including a total of 226,196 individuals from different European populations: 18,145 female PD cases, 95,558 female controls, 28,747 male PD cases, and 83,746 male controls. Results: We observed a high genetic correlation between the male and female PD meta-analyses (rg = 0.909, SE = 0.0403; p = 8.03E-113), and the heritability estimates were comparable between sexes (~10% in males and ~11% in females) and similar to estimates from prior sex-combined analyses. Our sex-stratified GWAS identified 57 genome-wide significant association signals, including five novel risk loci, three of which reached genome-wide significance in males only ( Conclusions: Overall, PD genetic architecture appears broadly similar between females and males, but the identification of five novel loci and significant differences at select regions highlights the value of sex-stratified analyses for uncovering additional genetic contributors to PD risk beyond those detected in combined analyses.
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