Investigating modifiable pathways in psoriasis: A Mendelian randomization study

Christos V Chalitsios; Andrea Georgiou; Emmanouil Bouras; Evangelos Evangelou; Dipender Gill; Kostas K Tsilidis; Ioanna Tzoulaki

doi:10.1016/j.jaad.2022.11.010

Investigating modifiable pathways in psoriasis: A Mendelian randomization study

J Am Acad Dermatol. 2023 Mar;88(3):593-601. doi: 10.1016/j.jaad.2022.11.010. Epub 2022 Nov 9.

Authors

Christos V Chalitsios¹, Andrea Georgiou², Emmanouil Bouras², Evangelos Evangelou³, Dipender Gill⁴, Kostas K Tsilidis⁵, Ioanna Tzoulaki⁶

Affiliations

¹ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece. Electronic address: christos.chalitsios@uoi.gr.
² Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
³ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece; Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK; Institute of Biosciences, University Research Center of Ioannina, University of Ioannina, Ioannina, Greece.
⁴ Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK.
⁵ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece; Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK.
⁶ Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece; Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK; Institute of Biosciences, University Research Center of Ioannina, University of Ioannina, Ioannina, Greece; BHF Centre of Excellence, School of Public Health, Imperial College London, London, UK.

PMID: 36370904
DOI: 10.1016/j.jaad.2022.11.010

Abstract

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.

Keywords: Mendelian randomization; epidemiology; genetics; modifiable factors; psoriasis; risk.

MeSH terms

Adult
Body Mass Index
Child
Educational Status
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis*
Obesity
Odds Ratio
Polymorphism, Single Nucleotide
Psoriasis*