Establishing a robust triangulation framework to explore the relationship between hearing loss and Parkinson's disease.

The relationship between hearing loss (HL) and Parkinson's disease (PD) remains unclear. Using individual-level and summary-level data from the UK Biobank and the largest genome-wide association studies, we examined this link through observational, Mendelian randomization and genetic pleiotropy analyses. Among 158,229 participants, PD risk rose with HL severity especially in elder and males, and hearing aids significantly reduced PD risk in males. Although our results did not support a causal association, genetic correlation analysis suggested a localized genetic overlap (17q21.31). We identified 1545 SNPs and 63 genes with pleiotropic effects on HL and PD, including 79 novel SNPs across 6 loci, with 3 showing strong co-localization. These loci were enriched in key tissues like brain, heart, liver and pancreas, linked to the dihydrolipoyl dehydrogenase complex pathway, and targeted by drugs such as Warfarin and Phenprocoumon. Overall, this study reveals the risk association, genetic basis, and pleiotropic loci connecting HL and PD.