Causal association between 3 adiposity indices and 5 infectious diseases: A Mendelian randomization study

Abstract

Previous studies on the association between adiposity indices and risk of infection have been inconsistent. To investigate the causality between different adiposity indices (body mass index [BMI], waist circumference [WC], and hip circumference [HC]) and the risk of infection (sepsis susceptibility (SS), sepsis mortality (SM), cholecystitis, intestinal infections, infections of the skin and subcutaneous tissue [SSTI], and acute lower respiratory infections). Mendelian randomization (MR) analysis was conducted to explore the causality between the 3 adiposity indices and the risk of 5 infectious diseases. Twenty-eight MR analyses were conducted to evaluate the final results, comprising 18 forward univariate MR, 5 reverse univariate MR, and 5 multivariable MR (MVMR) analyses. Data on adiposity indices and infections were obtained from the UK Biobanks, FinnGen Biobanks, Medical Research Council Integrative Epidemiology Unit, and within the family genome-wide association study consortium. Preliminary genetic variants associated with BMI (n = 11), WC (n = 374), and HC (n = 420) were selected as instrumental variables. The inverse-variance weighted (IVW) method combined with different types of MR methods was used to enhance the robustness of the final results. The statistical significance threshold was corrected using the Bonferroni method. The MVMR-IVW (random) analysis revealed that only WC had a significant and independent causal association with SS (odds ratio [OR] = 1.95; 95% confidence interval [CI]: 1.41-2.69; P < .001), SM (OR = 3.23; 95% CI: 1.52-6.86; P = .002), cholecystitis (OR = 1.87; 95% CI: 1.36-2.55; P < .001), and SSTI (OR = 1.74; 95% CI: 1.26-2.41; P = .001). These results were confirmed by other MVMR methods (least absolute shrinkage and selection operator regression, and MVMR-robust). Neither pleiotropy nor reverse causality was detected. WC may predict infectious disease risk more efficiently than other indices, and controlling WC may help decrease the risk of infectious diseases. Future long-term prospective studies are needed to explore the associations between dynamic adiposity indices and diverse infectious diseases in different populations.

Keywords: Mendelian randomization; adiposity indices; body mass index; hip circumference; infections; waist circumference.