Genome-wide cross-trait analysis to compare genetic architecture between Parkinson’s disease and kidney-related traits

Abstract Epidemiological studies link kidney function to Parkinson’s disease risk, but the genetic basis of this relationship remains unclear. Here, we leverage genome-wide association data for Parkinson’s disease and five UK Biobank-derived kidney-related traits in individuals of European ancestry, combining genetic correlation, pleiotropy mapping, colocalization and enrichment across sex-combined and sex-stratified analyses. Genome-wide genetic correlations with Parkinson’s are modest, with only a significant correlation with urinary potassium-to-creatinine ratio significant, yet we identify shared loci across 9 of 15 trait pairs. Resolving these loci, the two traits are more often driven by different causal variants within a shared region than by the same variant. Four loci carry a shared causal variant, implicating BIN3 , MSRA and TNK2 in protein quality control. These findings provide evidence for shared genomic loci between Parkinson’s disease and kidney function, offering specific loci and biological pathways for future investigation of the kidney-brain axis in neurodegeneration.