Observational studies have consistently reported associations between oral lichen planus (OLP) and psychological distress, yet whether these relationships are causal remains uncertain. We performed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal effects of depressive traits and anxiety-stress-related disorders (ASRD) on OLP. Genetic instruments for depressive traits (n = 500,199) and ASRD (n = 31,885) were obtained from the largest available genome-wide association study (GWAS) meta-analyses of European ancestry. Summary-level data for OLP were derived from the FinnGen R8 release, including 1,073 cases and 341,426 controls. Causal estimates were primarily calculated using the inverse-variance weighted (IVW) method, complemented by weighted median, MR-Egger, MR-PRESSO, leave-one-out analyses, and PhenoScanner searches to evaluate robustness and horizontal pleiotropy. The IVW results suggested a significant causal effect of ASRD on OLP risk (odds ratio 1.20, 95% CI 1.02-1.42), whereas no evidence supported a causal association between depressive traits and OLP (0.155 ≤ p ≤ 0.694). Reverse MR analyses did not indicate that genetic liability to broad depression, major depressive disorder, or ASRD increased OLP risk (0.052 ≤ p ≤ 0.793). Sensitivity analyses yielded consistent findings, and exclusion of pleiotropic SNPs did not materially alter the results. These findings support a potential causal role of ASRD in OLP pathogenesis and suggest that psychological factors related to stress and anxiety may warrant consideration in the clinical management of OLP.
Yuan et al. (Fri,) studied this question.