Psychological distress and oral lichen planus: A bidirectional Mendelian randomization study

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.