A LARGE two-sample Mendelian randomisation (MR) study provides strong genetic evidence that increased body mass index (BMI) causally increases the risk of hidradenitis suppurativa (HS), while the role of smoking remains unclear. The study also identifies inflammatory bowel disease (IBD) as a potential causal risk factor for HS, further highlighting shared inflammatory pathways between these conditions.
Hidradenitis Suppurativa: Uncertain Role of Lifestyle Risk Factors
HS is a chronic inflammatory skin disease often associated with smoking and obesity, although whether these relationships are causal has remained unclear. To address this, the researchers used MR methods, which leverage genetic variants as proxies for exposures, helping to reduce confounding and reverse causation seen in observational studies.
Genetic Approaches to Understanding Hidradenitis Suppurativa Risk
The investigators analysed genome-wide association study (GWAS) data from up to 3.6 million individuals of White European ancestry. HS genetic data included 4,814 cases and more than 1.2 million controls from Denmark, Iceland, Finland, the UK, and the US. Genetic instruments for BMI, smoking, psoriasis, IBD, and systemic sclerosis (SSc) were derived from large international GWAS consortia.
Genetic correlation analyses showed significant correlations between HS and BMI, smoking, psoriasis, and IBD, but not SSc. In MR analyses, higher BMI demonstrated a robust causal association with HS risk. Each genetically predicted unit increase in BMI was associated with a 20% increase in the odds of developing HS (OR 1.20; 95% CI 1.17–1.23; p<0.001), with no evidence of pleiotropy, supporting the validity of the finding.
Smoking initially showed a significant causal estimate; however, this association became inconclusive in sensitivity analyses, suggesting insufficient power or potential bias. As a result, the authors caution against drawing firm conclusions regarding smoking as a causal risk factor for HS based on the current genetic evidence.
Among the inflammatory diseases examined, IBD showed a clear causal relationship with HS (OR 1.20; 95% CI 1.15–1.24; p<0.001), whereas psoriasis and SSc did not demonstrate consistent causal effects in MR analyses.
The authors conclude that increased BMI and IBD are likely causal contributors to HS development. These findings reinforce the importance of weight management in patients at risk of HS and suggest that clinicians should remain vigilant for HS in individuals with IBD. Importantly, the study provides genetic evidence to support lifestyle-focused prevention strategies in HS management.
Reference
Anderson RK et al. Hidradenitis Suppurativa and Smoking, Obesity, Psoriasis, Inflammatory Bowel Disease, and Systemic Sclerosis: Results From A 2-Sample Mendelian Randomization Study. JAMA Dermatol. 2025;doi: 10.1001/jamadermatol.2025.5010
