Causal associations between food intakes and autoimmune skin diseases: A 2-sample Mendelian randomization study

Autoimmune skin diseases, such as bullous pemphigoid, pemphigus, lupus erythematosus, vitiligo, psoriasis, and atopic dermatitis, are chronic conditions driven by dysregulated immune responses. While emerging evidence suggests a potential role of food intakes in modulating these diseases through immune and inflammatory pathways, the causal relationships remain unclear due to limitations of observational studies. This study employed a 2-sample Mendelian randomization (MR) approach to evaluate the causal effects of 25 food intakes on the risk of autoimmune skin diseases, using genetic variants as instrumental variables. Exposure data were derived from the UK Biobank, and outcome data were obtained from the FinnGen Biobank. The inverse variance weighted method, complemented by MR-Egger, weighted median, and MR-PRESSO analyses, identified significant causal associations. After Bonferroni correction for multiple testing (P < 4 × 10⁻⁴), no associations remained statistically significant. However, several nominally significant (P < .05) associations were identified. Genetically predicted oily fish intake was inversely associated with bullous pemphigoid, and melon intake with lupus erythematosus. Cereal, milk, poultry, and salted nuts intake showed inverse associations with pemphigus. Tea and salted nuts intake were associated with reduced atopic dermatitis risk, while cheese, dried fruit, and salted nuts intake were associated with lower psoriasis risk. Conversely, alcohol and poultry intake were associated with increased psoriasis risk. No causal associations were observed for vitiligo. Sensitivity analyses (including MR-Egger intercept, Cochran Q test, MR-PRESSO, and leave-one-out analysis) supported the robustness and directionality of these nominally significant effects, with no evidence of directional pleiotropy. Multiple nominally significant associations were observed, suggesting potential protective roles for foods such as oily fish, nuts, fruits, and tea in specific autoimmune skin conditions, and a potential risk associated with alcohol consumption for psoriasis. These suggestive findings highlight the need for further investigation in larger cohorts to clarify the role of diet in the prevention and management of autoimmune skin conditions.