Does greater adiposity increase blood pressure and hypertension risk?: Mendelian randomization using the FTO/MC4R...

Area of Science:

• Cardiovascular Epidemiology
• Human Genetics
• Metabolic Disorders

Background:

• Elevated blood pressure is a major risk factor for cardiovascular events such as myocardial infarction and stroke.
• Observational studies suggest a causal link between body mass index (BMI) and hypertension, but are susceptible to confounding and reverse causation.
• Unbiased estimation of the association between adiposity and blood pressure is crucial for public health interventions.

Purpose of the Study:

• To estimate the unconfounded and unbiased association between body mass index (BMI) and blood pressure using instrumental variable methods.
• To confirm observational findings regarding the relationship between BMI and hypertension, mitigating potential biases.

Main Methods:

• Utilized instrumental variable analysis within the Copenhagen General Population Study.
• Employed specific genetic variants, rs9939609 (FTO) and rs17782313 (MC4R), as instrumental variables for BMI.
• Accounted for participants receiving antihypertensive medication through appropriate adjustments.

Main Results:

• Confirmed a positive association between BMI and blood pressure, free from confounding and reverse causation.
• A 10% increase in BMI was associated with a 3.85 mm Hg rise in systolic blood pressure (P=0.0002).
• A 10% increase in BMI was associated with a 1.79 mm Hg rise in diastolic blood pressure (P=0.002).

Conclusions:

• Body mass index has a significant causal impact on blood pressure.
• The observed associations are substantial, highlighting the potential for considerable reductions in cardiovascular morbidity.
• Reducing body mass index presents a key strategy for mitigating hypertension and its associated health risks.