Causal link identified in instrumental variable analyses is consistent with observational studies
WEDNESDAY, May 2 (HealthDay News) -- The positive association between body mass index (BMI) and ischemic heart disease (IHD) is likely to be causal, according to a study published online May 1 in PLoS Medicine.
Using data from 75,627 participants from three studies in Copenhagen, Børge G. Nordestgaard, M.D., from the Copenhagen University Hospital in Denmark, and colleagues investigated whether the positive association between BMI and IHD is causal. BMI was measured, IHD events ascertained, and FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238) were genotyped. Using the genotypes as a combined allele score, the allele score-BMI and allele score-IHD associations were calculated and used in instrumental variable analyses to estimate the causal odds ratio (OR) between BMI and IHD, which was then compared with observational analyses.
In the observational analyses, the researchers found that, for every 4 kg/m² increase in BMI, the OR for IHD was 1.26. A one-unit allele score increase correlated with an increase in BMI (0.28 kg/m²) and an OR for IHD of 1.03 (95 percent confidence interval, 1.01 to 1.05). For those carrying all six alleles, the average increase in BMI was 1.68 kg/m² and the odds for IHD increased by 18 percent. For a 4 kg/m² increase in BMI, the causal OR for IHD was 1.52 in instrumental variable analysis.
"For every 4 kg/m² increase in BMI, observational estimates suggested a 26 percent increase in odds for IHD while causal estimates suggested a 52 percent increase," the authors write. "These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia, and type 2 diabetes."
One author disclosed being on the PLoS Medicine Editorial Board.
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