Investigating modifiable pathways in psoriasis: A Mendelian randomization study

Background: Potentially modifiable risk factors have previously been investigated only in conventional observational studies. Objective: To assess whether genetically predicted exposures to modifiable factors are associated with the risk of psoriasis. Methods: Two-sample Mendelian randomization (MR) analysis. Results: An increased risk of psoriasis was noted for genetically predicted lifetime smoking index (odds ratio [OR]MR-IVW = 2.11; 95% confidence interval [CI], 1.28-3.51), childhood (OR MR-IVW = 1.40; 95% CI, 1.14-1.71) and adult body mass index (OR MR-IVW = 1.63; 95% CI, 1.32-2), waist (OR IVW = 1.86; 95% CI, 1.31-2.64), and hip circumference (OR MR-IVW = 1.55; 95% CI, 1.15-2.07). Protective association was also reported between genetically predicted longer sleep duration (OR MR-IVW = 0.56; 95% CI 0.37-0.84) and increased years of education (OR MR-IVW = 0.78; 95% CI, 0.62-0.98). This effect of education persisted in multivariable MR after adjusting for genetic predictors of smoking and adult body mass index (ORMVMR-IVW = 0.72; 95% CI, 0.56-0.92). Limitations: It was not possible to stratify for psoriasis severity. Conclusion: Smoking cessation and prevention of obesity are important strategies for decreasing the incidence of psoriasis. Similarly, targeting education inequality is expected to lead further to reductions in cases of psoriasis. ( J Am Acad Dermatol 2023;88:593-601.)