Reproductive Traits Linked to Psoriasis Risk But Mediated By BMI, Education

New research suggests adiposity and access to education may be clinically relevant modifiable mediators of psoriasis risk attributable to reproductive factors.1

The 2-sample and 2-step Mendelian randomization (MR) analysis explored the impact of major reproductive factors on the risk of psoriasis, including overall psoriasis, psoriasis vulgaris (PV), and psoriatic arthritis (PsA), while accounting for the potential mediation effect of 4 confounders: body mass index (BMI), years of education, tobacco use, and alcohol consumption level.1

“To the best of our knowledge, the association and mechanisms involved in the relationship between reproductive factors and psoriasis have not been fully elucidated, and there are no studies of causal intermediates or mediators,” Yajia Li, of the department of dermatology and the National Clinical Research Center for Geriatric Disorders at Xiangya Hospital in China, and colleagues wrote.1

Psoriasis affects an estimated 3% of the adult population ≥ 20 years of age in the US, or more than 7.5 million adults.2 Understanding modifiable risk factors is essential for preventing the onset and managing the adverse health outcomes associated with psoriasis. While hormone-induced factors have previously been identified, studies investigating the association between modifiable reproductive factors and the incidence of psoriasis are sparse.1

To explore the association between reproductive traits and risk of psoriasis and the mediated proportion of the total causal effects of known confounders, investigators conducted a 2-sample MR study using summarized statistics from the genome-wide association studies (GWAS) conducted in reproductive traits as well as GWAS data on overall psoriasis, PsA, and PV.1

Investigators identified 7 different factors for the exposure datasets, including age at menarche (AMA, 243,944 individuals), age at menopause (AMP, 143,819 individuals), age at first birth (AFB, 542,901 individuals), age at last live birth (ALB, 170,248 individuals), number of live births (NEB, 250,782 individuals), age at first sexual intercourse (AFS, 397,338 individuals), and lifetime number of sexual partners (NSP, 378,882 individuals).1

Psoriasis (216,752 individuals including 4510 cases and 212,242 controls), PsA (213,879 individuals including 1,637 cases and 212,242 controls), and PV (215,044 individuals including 2802 cases and 212,242 controls) data were obtained from the FinnGen Biobank Analysis Consortium database.1

Acknowledging the complex clinical and genetic backgrounds of the psoriasis cases, investigators merged 4 potential confounders previously shown to be associated with the exposure and outcome to construct an multivariable MR and a 2-step mediation MR model to adjust the mediation effect; these included BMI (99,998 individuals), years of education (766,345 individuals), tobacco consumption (249,752 individuals), and alcohol consumption level (462,346 individuals).1

Strongly associated single nucleotide polymorphisms were filtered out using a stringent genome-wide significance threshold of P < 5 × 10-8 to ensure the relevance assumption.1

In univariable MR analysis, only AFS demonstrated a significant protective effect on psoriasis (odds ratio [OR], 0.54; 95% CI, 0.41-0.72; P = .000), consistent with the results obtained using the CAUSE method (OR, 0.71; 95% CI, 0.63-0.80; P = .002). Of note, this causal effect lost significance after correcting BMI (OR, 0.66; 95% CI, 0.48-1.12; P = .113) and education (OR, 0.71; 95% CI, 0.48-1.06; P = .096), and further analysis revealed 36.13% and 47.79% of this effect was mediated through BMI and educational attainment, respectively.1

Additionally, AFB showed a significant negative association with PsA (OR, 0.76; 95% CI, 0.64-0.92; P = .003) in the univariable MR, consistent with the results of the CAUSE method (OR, 0.87; 95% CI, 0.82-0.92; P = .038). Further 2-step analysis revealed a partial mediating effect of BMI on the association between AFB and PsA, with a 49.61% proportion of the mediation attributable to BMI.1

AFS also had a significant negative effect on PV (OR, 0.38; 95% CI, 0.27-0.55; P <.001), which aligned with findings from the CAUSE method (OR, 0.60; 95% CI, 0.55-0.65; P <.001). A partial but nonsignificant mediating effect was found for BMI on AFS-PV (indirect effect OR, 0.78; 95% CI, 0.45-1.33; P = .352; proportion of mediation, 26.27%), while the direct effect of AFS (OR, 0.44; 95% CI, 0.30 to 0.66; P <.001) was statistically significant.1

“Greater efforts to reduce adiposity and improve access to education appear to be clinically relevant,” investigators concluded.1 “In addition, further research is needed to identify other environmental risk factors that act as potentially modifiable mediators of psoriasis. Modifying these factors may help substantially reduce the burden of psoriasis risk that is attributable to reproductive factors.”

References

1. Li Y, Li Q, Cao Z, et al. The Impact of Reproductive Traits on Psoriasis Risk is Mediated by Education Attainment and Body Mass Index: A Mendelian Randomization Study. Biomedical and Environmental Sciences. doi:10.3967/bes2024.122

2. National Psoriasis Foundation. Prevalence of Psoriasis. Accessed April 22, 2025. https://www.psoriasis.org/prevalence-of-psoriasis/