Summary
This Mendelian randomization study of 14 prospective cohorts and multiple disease consortia (66,842 CHD cases, 12,389 ischaemic stroke cases, 34,840 type 2 diabetes cases) establishes causal associations between both general and central adiposity and cardiometabolic disease. Central adiposity (WHRadjBMI) showed stronger causal effects on ischaemic stroke risk (48% excess per 1 SD) compared to general adiposity, whilst both measures exerted large causal effects on type 2 diabetes risk. The findings suggest that adiposity distribution matters differentially across disease endpoints, with implications for risk stratification and preventive strategies.
Regional applicability
The findings are directly applicable to UK population health strategy, given the reliance on BMI for obesity screening and cardiovascular risk assessment in NHS guidance. The demonstration that central adiposity (waist-to-hip ratio) has stronger causal effects on stroke risk may inform refinement of UK cardiovascular risk prediction tools and obesity management priorities.
Key measures
Odds ratios per 1 SD increase in WHRadjBMI (≈0.08 U) and BMI (≈4.6 kg/m²); 95% confidence intervals for CHD, ischemic stroke, haemorrhagic stroke, and type 2 diabetes mellitus; associations with intermediate cardiometabolic traits
Outcomes reported
The study quantified causal associations between central adiposity (waist-to-hip ratio adjusted for BMI) and general adiposity (BMI) with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus using Mendelian randomization. Secondary outcomes included 18 cardiometabolic traits and intermediate mechanisms including lipids, glycaemic traits, and inflammatory markers.
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