Does higher BMI causally raise heart disease risk?
Genetic instruments for BMI suggest a causal increase in ischemic heart disease risk larger than simple observational estimates.
Source
The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach
Study at a glance
- Design
- Mendelian randomisation — Allele-score MR of BMI on ischemic heart disease in three Danish samples
- N
- N=75627 · CGPS n = 54,613; CCHS n = 10,474; CIHDS n = 10,540; all of Danish descent
- Population
- White adults of Danish descent in two general-population studies and an IHD case collection
- Outcome
- Causal effect of elevated BMI on ischemic heart disease risk
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Does higher BMI causally raise heart disease risk?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Observational OR ~1.26 pooled; CGPS 1.23
In the general population, for one standard deviation (4 kg/m 2 ) increase in BMI, the observational ORs for IHD were 1.23 (95% CI 1.19–1.28) for the CGPS and 1.31 (95% CI 1.23–1.39) for the CCHS ().
What analytic framework estimates causality?
An alternative approach free of confounding, reverse causation, and bias is that of Mendelian randomisation .
What they did
Using Copenhagen cohorts, investigators compared observational BMI–IHD associations with Mendelian randomisation estimates based on FTO, MC4R, and TMEM18 alleles as instruments for BMI.
What they found
Observationally, each 4 kg/m² BMI related to about 26% higher IHD odds; the causal instrumental-variable OR was about 1.52 (52% higher). Alleles raised BMI by ~0.28 kg/m² each.
The limits
What it doesn't show
MR supports causality but does not identify which intermediate pathways fully mediate BMI’s effect or the best weight-loss treatment.
Key terms
- Mendelian randomisation
- Using genetic variants as instrumental variables to infer causal effects of modifiable risks.
- BMI
- Body mass index, weight relative to height, used as an adiposity marker.
- IHD
- Ischemic heart disease from coronary atherosclerosis.
- Instrumental variable
- A factor that affects outcome only through the exposure, here adiposity alleles.
- Confounding
- Bias when lifestyle/SES factors distort observational BMI–disease links.
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Mendelian randomisation here tests causality of:
Common questions
Why use genetics?
Alleles are assigned at conception, reducing confounding and reverse causation.
Which genes?
FTO, MC4R, and TMEM18 variants in an allele score.
Observational vs causal?
About 26% vs 52% higher IHD risk per 4 kg/m² BMI.
Policy angle?
Supports reducing BMI even modestly for heart-disease prevention.
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