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(Hypertension. 2009;54:84.)
© 2009 American Heart Association, Inc.

Original Articles

Does Greater Adiposity Increase Blood Pressure and Hypertension Risk?

Mendelian Randomization Using the FTO/MC4R Genotype

Nicholas J. Timpson; Roger Harbord; George Davey Smith; Jeppe Zacho; Anne Tybjærg-Hansen; Børge G. Nordestgaard

From the Medical Research Council Centre for Causal Analysis in Translational Epidemiology (N.J.T., G.D.S.) and Department of Social Medicine (R.H.), Bristol University, Bristol, United Kingdom; Department of Clinical Biochemistry (J.Z., B.G.N.) and Copenhagen General Population Study (J.Z., A.T-H., B.G.N.), Herlev Hospital, Herlev, Denmark; Department of Clinical Biochemistry (A.T-H.), Rigshospitalet, Copenhagen, Denmark; and the Faculty of Health Sciences (J.Z., A.T-H., B.G.N.), Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.

Correspondence to Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail brno{at}heh.regionh.dk

Elevated blood pressure increases the risk of experiencing cardiovascular events like myocardial infarction and stroke. Current observational data suggest that body mass index may have a causal role in the etiology of hypertension, but this may be influenced by confounding and reverse causation. Through the use of instrumental variable methods, we aim to estimate the strength of the unconfounded and unbiased association between body mass index/adiposity and blood pressure. We explore these issues in the Copenhagen General Population Study. We used instrumental variable methods to obtain estimates of the causal association between body mass index and blood pressure. This was performed using both rs9939609 (FTO) and rs17782313 (MC4R) genotypes as instruments for body mass index. Avoiding the epidemiological problems of confounding, bias, and reverse causation, we confirmed observational associations between body mass index and blood pressure. In analyses including those taking antihypertensive drugs, but for whom appropriate adjustment had been made, systolic blood pressure was seen to increase by 3.85 mm Hg (95% CI: 1.88 to 5.83 mm Hg) for each 10% increase in body mass index (P=0.0002), with diastolic blood pressure showing an increase of 1.79 mm Hg (95% CI: 0.68 to 2.90 mm Hg) for each 10% increase in body mass index (P=0.002). Observed associations are large and illustrate the considerable benefits in terms of reductions in blood pressure–related morbidity that could be achieved through a reduction in body mass index.

Key Words: epidemiology • genetics • blood pressure • obesity • fat mass