Summary
This large multi-consortium Mendelian randomization meta-analysis quantified causal relationships between adiposity measures and cardiometabolic disease using genetic variants from 14 prospective studies and multiple disease registries totalling over 66,000 CHD cases, 12,000 stroke cases, and 34,000 type 2 diabetes cases. Both general adiposity (BMI) and central adiposity (WHRadjBMI) showed causal effects on coronary heart disease risk, though only WHRadjBMI increased ischaemic stroke risk, whilst both substantially elevated type 2 diabetes risk. The analysis identified shared biological pathways including left ventricular hypertrophy, glycaemic dysfunction, inflammation (interleukin-6), and dyslipidaemia.
Regional applicability
These findings are directly applicable to United Kingdom population health policy and clinical practice, as the study includes substantial UK cohort data and addresses common cardiometabolic diseases prevalent in the UK. The quantified causal effects provide evidence to support weight management and cardiovascular risk reduction strategies in UK health services and public health interventions.
Key measures
Odds ratios per 1 standard deviation increase in WHRadjBMI and BMI for CHD, ischemic stroke, type 2 diabetes mellitus; associations with left ventricular hypertrophy, glycemic traits, interleukin-6, circulating lipids, and carotid intima-media thickness
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 associations with 18 cardiometabolic traits and biomarkers.
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