Blog | Thursday, May 3, 2012

QD: News Every Day--Genes have causal links between BMI, heart disease

Researchers studied genetic variants to establish a causal link to the long observed association between body mass and ischemic heart disease.

Researchers used "Mendelian randomization" to find that every 4 kg/m2 increase in body-mass index (BMI) leads to a 26% increase in odds for ischemic heart disease. Three common genetic variants combined, FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238), increased the risk of each 4 kg/m2 to 52%.

Editors at PloS Medicine wrote that, because gene variants are inherited randomly with respect to conventional confounding factors and are not subject reverse causation, using them as markers allows researchers to learn whether obesity is causally involved in ischemic heart disease.

The researchers analyzed data from two population-based studies in which adults were physically examined and answered a lifestyle questionnaire before being followed to see how many developed ischemic heart disease. They also analyzed data from a case-control study. Results appeared online at PloS Medicine.

Among 75,627 individuals from the three studies, 11,056 developed ischemic heart disease events. The odds ratio (OR) for ischemic heart disease was 1.26 (95% confidence interval [CI], 1.19 to 1.34) for every 4 kg/m2 increase in BMI.

A one-unit allele score increase associated with a 0.28 kg/m2 (95 CI%, 0.20 to 0.36) increase in BMI and an OR for ischemic heart disease of 1.03 (95% CI, 1.01 to 1.05) (corresponding to an average 1.68 kg/m2 BMI increase and 18% increase in the odds of ischemic heart disease for those carrying all six BMI-increasing alleles). In instrumental variable analysis using the same allele score the causal ischemic heart disease odds ratio for a 4 kg/m2 increase in BMI was 1.52 (95% CI, 1.12 to 2.05).

Authors concluded, "These data add novel evidence to support a causal link between increased BMI and increased IHD [ischemic heart disease] risk, while the mechanism of this effect is likely to be operating through intermediate factors. In the context of recent, high impact, observational findings, this work has important policy implications for public health given the continuous nature of the BMI-IHD association, the modifiable nature of BMI, and the likely benefits of reducing BMI even by moderate levels."