Overlapping Genetic Architecture between Parkinson Disease and Melanoma

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10 to 0.24;P= 4.09 × 10-06) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22;P= 7.87 × 10-04), and highlight seven genes includingPIEZO1, TRAPPC2L, andSOX6as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.