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 (OR _MVMR-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.
Competing Interests: Conflicts of interest D.G is employed part-time by Novo Nordisk, outside of the submitted work. The other authors have none to disclose.
(Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)