Higher BMI, IBD Linked to Hidradenitis Suppurativa Risk via Mendelian Randomization

Increased body mass index (BMI) and inflammatory bowel disease (IBD) were found to have causal effects on the risk of hidradenitis suppurativa (HS), according to a new study published in JAMA Dermatology.¹

The study aimed to investigate relationships between HS and BMI, smoking, and 3 inflammatory diseases (psoriasis, IBD, and systemic sclerosis [SSc]). Prior research has associated HS with genetic factors, lifestyle, environmental exposures, and various other conditions like obesity and tobacco smoking, but more research is needed to identify potential causality.^1,2 This research has the potential to provide physicians with vital information to reassure their patients with HS of the genetic predispositions and lifestyle exposures that may explain or aggravate their symptoms. Dermatologists have often pointed out that balancing genetic factors and lifestyle management helps patients feel more in control of their lives while managing this disease.²

The study used Mendelian randomization (MR) to investigate causal effects of potential risk factors as opposed to associations.¹ MR is able to simulate a randomized clinical trial by assessing naturally occurring genetic differences that influence the likelihood of potential causal risk factors, thus mitigating inherent risk or confounding and reverse causation. By relying on 3 core assumptions, MR ensures unbiased causal estimates rather than an estimate of phenotypic correlation. The 3 core assumptions are the relevance assumption, that the genetic variants are robustly associated with the exposure; the independence assumption, that these variants are not related to confounding factors influencing both the exposure and the outcome; and the exclusion assumption, that the genetic variants affect the outcome only through the exposure and no alternative pathways.

Genetic correlation (r_g) between HS and the 5 exposure phenotypes (BMI, smoking, psoriasis, IBD, and SSc) was estimated through cross-trait linkage disequilibrium (LD) score regression; LD data were downloaded from the BROAD Institute. Association results for HS were derived from the HS meta-analysis. For BMI, restricted meta-analysis was used from the UK Biobank and the GIANT consortium. For smoking, results were used from previous studies. Meta-analysis data were used for psoriasis, IBD, and SSc.

The analyses used 1.2 million common variants from the meta-analysis of HS, BMI, and smoking. These data revealed moderate genetic correlations between HS and BMI (r_g = 0.36 [P < .001]) and between HS and smoking (r_g = 0.33 [P < .001]). The inverse variance weighted MR of BMI and HS was consistent with a causal relationship, but the result for smoking and HS was less clear. The estimated genetic correlation between HS and IBD was r_g = 0.25 (P < .001), r_g = 0.34 (P < .001) for psoriasis, and r_g = 0.33 (P = .22) for SSc.

“The findings of this 2-sample MR study on the causal relationship among 5 phenotypes: BMI, smoking, psoriasis, IBD, and SSc (exposures), and HS (outcome), support a causal effect of both BMI and IBD on HS,” the study authors explained.

The study was limited by the lack of generalizability, as all the cohorts were of White European ancestry. Additionally, possible sample overlap between cohorts could introduce residual bias despite mitigation efforts, and sensitivity analyses did not confirm a causal role for smoking. Limited data on disease severity and the potential for residual pleiotropy or heterogeneity restrict the strength and interpretation of the causal estimates.

References

1. Kjærsgaard Andersen R, Riis PT, Zachariae C, et al. Hidradenitis suppurativa and smoking, obesity, psoriasis, inflammatory bowel disease, and systemic sclerosis: results from a 2-sample Mendelian randomization study. JAMA Dermatol. Published online December 17, 2025. doi:10.1001/jamadermatol.2025.5010

2. McCrear S, Mayo T. Emerging therapies for managing hidradenitis suppurativa: Tiffany Mayo, MD. AJMC^®. October 10, 2025. Accessed December 17, 2025. https://www.ajmc.com/view/emerging-therapies-for-managing-hidradenitis-suppurativa-tiffany-mayo-md