Does greater adiposity increase blood pressure and hypertension risk?: Mendelian randomization using the FTO/MC4R genotype.
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.
Timpson
Nicholas J
NJ
Medical Research Council Centre for Causal Analysis in Translational Epidemiology, Bristol University, United Kingdom.
Harbord
Roger
R
Davey Smith
George
G
Zacho
Jeppe
J
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D050154:Adiposity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001794:Blood Pressure; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D012307:Risk Factors; D012907:Smoking; D049629:Waist-Hip Ratio; D055815:Young Adult
C470072:MC4R protein, human; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human