Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women
An erratum to this article was published (Diabetologia, Sep 2024 ↗)
Authors' conclusion
We describe the shapes of causal effects of BMI on cardiometabolic diseases and risk factors, and report sex differences in the causal effects of BMI on LDL-cholesterol. We found evidence of non-linearity in the causal effect of BMI on diseases and risk factor biomarkers. Reducing excess adiposity is highly beneficial for health, but there is greater need to consider biological sex in the management of adiposity.
Study context
- Comparison
- Genetically predicted BMI and cardiometabolic diseases and risk factors, by sex
- Outcome
- Causal association of BMI with cardiometabolic diseases
Methodological detailstwo-stage least-squares, polygenic risk score for BMI as instrumental variable, non-linear Mendelian randomisation (MR) fractional polynomial method, piecewise MR
- Two-stage least-squares
- Polygenic risk score for BMI as instrumental variable
- Non-linear MR fractional polynomial method
- Piecewise MR
Performance
As reported in the abstract
- T2D, OR
- 3.10 (2.73, 3.53) (95% CI)
- Hypertension, OR
- 1.53 (1.44, 1.62) (95% CI)
- Coronary artery disease, OR
- 1.20 (1.08, 1.33) (95% CI)
- CKD, not associated, OR
- 1.08 (0.67, 1.72) (95% CI)
- Stroke, not associated, OR
- 1.08 (0.92, 1.28) (95% CI)
Further findings
Cardiometabolic risk factors
- Non-linear causal relationship between BMI and BP and other biomarkers except lipoprotein A
- P < 0.001
- BMI positively associated with glucose, HbA1c, triacylglycerol, systolic and diastolic BP
- BMI inversely associated with total cholesterol, LDL-C and HDL-C
- Piecewise MR results consistent with fractional polynomial results
Sex differences in causal effects of BMI
- Effect on coronary artery disease, total cholesterol and LDL-C differed in men and women; significant after multiple-testing control only for LDL-C
- P < 0.001
- Effect on coronary artery disease varied by menopause status in women
Original publication
Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women. Diabetologia. Published 12 October 2022. doi:10.
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