Higher Body Mass Index Is a Causal Risk Factor for Skin Infections: A Mendelian Randomisation Study Using <scp>UK</scp> Biobank and <scp>FinnGen</scp>

ABSTRACT Aims Infections remain a leading cause of mortality and morbidity globally. We aimed to evaluate the potential causal role of higher BMI on common bacterial, viral and fungal infections using Mendelian randomisation (MR). Material and Methods In UK Biobank ( N = 502 131, N = 230 542 with linked GP records), we tested observational associations and used one‐sample MR to test for a causal effect of BMI on common infections (skin infections, respiratory infections and urogenital infections) in primary care and hospital admissions. We additionally performed two‐sample MR using summary statistics from a BMI genome‐wide association study and infection outcomes from FinnGen ( N = 500 348). Results Higher BMI was observationally associated with all infection types. One‐sample MR demonstrated that higher BMI has a causal effect on skin infections in primary care (bacterial: Odds Ratio [OR] 1.37 [95% CI:1.24–1.53] per 5 kg/m2 increase in BMI, p &lt; 0.001, fungal: 1.34 [95% CI:1.18–1.53], p &lt; 0.001) and hospitalisation with skin infections (bacterial: OR 1.93 [95% CI:1.71–2.19] per 5 kg/m 2 increase in BMI, p &lt; 0.001, fungal: 2.81 [95% CI:1.58–4.97], p &lt; 0.001). Two‐sample MR provided further evidence of a causal effect that is robust to pleiotropy. MR suggests that the estimated causal effect of higher BMI on some respiratory infections may be biased by pleiotropy. Conclusions Mendelian randomisation provides strong evidence that higher BMI is a causal risk factor for bacterial and fungal skin infections. Weight loss interventions may help reduce the risk of both mild and severe bacterial and fungal skin infections and be targeted to those at highest risk.