Mendelian Randomization Analysis Supports Causal Effect of Type II Diabetes Mellitus on Onychomycosis

Introduction: Onychomycosis is common among adults with diabetes mellitus (DM). We used two-sample Mendelian randomization to estimate the causal effect of genetic risk for DM on onychomycosis and tinea skin infections in the All of Us Research Program. Methods: Onychomycosis and tinea corporis, pedis, manus, and cruris cases were identified using electronic health record data, and genetic instrument variables and summary statistics were collected from a type II DM (T2DM) genome-wide association study (GWAS) meta-analysis. Results: Inverse variance weighted regression showed positive effect of T2DM genetic risk on onychomycosis (beta = 0.135, p = 1.86E−2), and weighted median regression produced a comparable estimate of effect size (beta = 0.148). There was no significant effect of T2DM on skin dermatophytosis. Conclusions: Our results suggest that T2DM has a positive causal effect on onychomycosis but not tinea skin infection risk. As onychomycosis may impair occupational function and increase risk for secondary soft tissue infections, patients with diabetes should be screened for onychomycosis and counseled on mitigating infection risk.