Abstract
BACKGROUND: Hypertension is a global health issue, and the risk factors include genetics, physical inactivity, and excess body fat (adiposity). Genetic predisposition to adiposity generally increases risk of hypertension. Several genetic variants have been identified to increase adiposity but unexpectedly reduce hypertension (favorable adiposity genes). Here, we tested the effect of these genetic variants on risk of hypertension in European ancestry participants under various scenarios of physical activity and body mass index. METHODS: Favorable adiposity genetic liability was estimated using previously identified genetic variants and their effect sizes. The study analyzed data from 210 290 unrelated participants in the UK Biobank. Logistic regression was used to examine the association between this genetic liability and hypertension (defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the use of antihypertensive medications). The analyses were conducted separately based on physical activity status (physically active and inactive) within low and high body mass groups. RESULTS: Individuals with high body mass, could reduce their risk of hypertension by up to 13% depending on the favorable adiposity genetic liability and physical activity status (P(adjusted)=5.44×10(-7)). In high body mass individuals, physical activity alone contributes to 5% to 7% reduction in risk of hypertension. CONCLUSIONS: The study provides evidence that the protective effect of favorable adiposity on hypertension risk varies according to body mass composition and physical activity status.