BMI, Inflammatory Bowel Disease Both Show Causal Effect on HS Development

Inflammatory bowel disease (IBD) and increased body mass index (BMI) are causally linked to patients’ risk of hidradenitis suppurativa (HS), new findings suggest.1

These new findings and their analysis were published in JAMA, with Rune Kjærsgaard Andersen, MD, PhD, from the Department of Dermatology and Allergy at Herlev and Gentofte Hospital in Denmark, as the corresponding author. Andersen et al highlighted the previous connections drawn between obesity and smoking to HS development, pointing to what had previously been a lack of a causal connection fully developed by researchers.2,3

“To investigate our primary objective, the causal effect of the environmental exposures on HS, we performed 2-sample MR analyses of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and smoking on HS,” Andersen and colleagues wrote.1

As a secondary aim, the investigators set out to assess a potential connection between HS and 3 inflammatory conditions: psoriasis, IBD, and systemic sclerosis (SSc).

Design and Findings on HS

The investigative team performed their Mendelian randomization (MR) analysis to assess the aforementioned 5 traits and HS as the study's outcome. Their analysis leveraged large genome-wide association study (GWAS) datasets which they noted were made up of individuals of White European ancestry for all phenotypes. Andersen et al noted their primary analyses were carried out in May 2024 and later given updates in May 2025.

Genetic correlation (rg), which ranges from −1 to 1 and reflects the extent of shared genetic architecture between 2 traits, was calculated by the investigators between HS and each exposure via the use of cross-trait linkage disequilibrium (LD) score regression. These analyses incorporated association statistics from approximately 1.2 million well-imputed genetic variants. Andersen and colleagues derived LD information from precomputed scores for White European populations provided by the Broad Institute.

Genome-wide significant single-nucleotide variants (SNVs) identified in the largest publicly available GWAS previously, or in consortium datasets, were implemented by the investigative team as instrumental variables for each exposure phenotype. The team collected HS data from a meta-analysis including 4814 individuals with HS and 1,216,105 control participants from Iceland, Denmark, Finland, the UK, and the US. The necessary BMI estimates were based on a White European–restricted meta-analysis of roughly 700,000 participants from the UK Biobank and the GIANT consortium.

For SSc, Andersen and coauthors used a publicly available meta-analysis of 9095 cases and 17,584 control participants of White European descent was used. Data on psoriasis came from a meta-analysis including 39,498 cases and 286,769 controls. Smoking-related genetic instruments were derived from a large analysis which looked into ever-regular smokers with never-regular smokers, encompassing 1,232,091 subjects. IBD data were sourced from the International IBD Genetics Consortium and included 38,155 cases and 48,485 controls.

Overall, the investigative team's genetic correlation analyses demonstrated significant shared genetic liability between HS and all exposures except SSc. They found positive correlations for BMI (rg = 0.36, P < .001), IBD (rg = 0.25, P < .001), smoking (rg = 0.33, P < .001), and psoriasis (rg = 0.34, P < .001). Conversely, the correlation with SSc was shown not to be statistically significant (rg = 0.33, P = .22).

Andersen et al's MR results supported a causal link between increased BMI and higher risk of HS, with the investigators pointing to an estimated effect size of β = 0.87, corresponding to an OR of 1.20 per unit increase in BMI (95% CI, 1.17–1.23; P < .001). In their sensitivity analyses, Andersen and colleagues did not identify evidence of directional pleiotropy (slope β = 0.91, P < .001; intercept P = .76). They also noted smoking initially demonstrated a significant causal estimate (β = 0.59, P < .001), but added the link was attenuated and became less definitive in sensitivity analyses.

Among the remaining immune-mediated conditions assessed by Andersen and coauthors, the data supported a causal role for IBD in development of HS (β = 0.18; OR = 1.20; 95% CI, 1.15–1.24; P < .001), and there was no indication of pleiotropic bias.

“Although initial MR analysis also found a causal effect of smoking on HS, this disappeared during subsequent sensitivity analysis,” the team concluded.1 “However, because none of the sensitivity analyses revealed signs of pleiotropic effects, the MR should be viewed as inconclusive rather than proof of no causal effect.”

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. Mintoff D, Agius R, Pace NP, et al. Obesity and hidradenitis suppurativa: targeting meta-inflammation for therapeutic gain. Clin Exp Dermatol. 2023 Aug 25;48(9):984-990. doi: 10.1093/ced/llad182. PMID: 37171791.

3. Happle R, König A. A lesson to be learned from Karl Marx: smoking triggers hidradenitis suppurativa. Br J Dermatol. 2008 Jul;159(1):255-6; author reply 256-7. doi: 10.1111/j.1365-2133.2008.08604.x. Epub 2008 Jul 1. PMID: 18489595.