Effects of Polygenic Risk Scores and Physical Activity on Blood Pressure Trajectories in Childhood, Adolescence, and Young Adulthood

BACKGROUND: Understanding the effects of genetics and lifestyle habits such as physical activity on blood pressure (BP) trajectories at an early age helps to improve understanding of the pathogenesis of hypertension over the life course. METHODS: BP was assessed twice (at baseline and follow-up) in prepuberty (n=1063; age 5-6 years; median follow-up, 4.72 years), puberty (n=2494; age 8-14 years; median follow-up, 3.00 years), and postpuberty (n=2549; age 15-20 years; median follow-up, 3.00 years). We calculated polygenic risk scores (PRSs) for BP based on the largest BP genome-wide association study and examined the associations of PRSs with BP trajectories in the 3 age epochs, using linear mixed models. RESULTS: One SD of PRSs was positively associated with 1.70, 1.65, and 2.92 mm Hg SBP level and 1.68, 0.85, and 1.18 mm Hg diastolic blood pressure (DBP) level at ages 5, 8, and 15 years, respectively. There was evidence of associations between PRSs and rates of change in SBP during puberty and DBP during postpuberty. During puberty, individuals in the highest quartile of systolic blood pressure (SBP)-PRS showed a 0.32 (95% CI, 0.02-0.63) mm Hg greater increase in SBP per year compared with those in the lowest quartile, while in postpuberty, those in the highest quartile of the DBP-PRS exhibited a 0.24 (95% CI, 0.02-0.45) mm Hg/y greater increase in DBP. Children who were physically active had, on average, 1.90 (95% CI, -3.77 to -0.03) mm Hg lower initial SBP than inactive children in puberty. No evidence was found for interactions of physical activity with PRS on BP levels or changes. CONCLUSIONS: Our study suggests that genetic influences on BP are evident as early as age 5 and extend to dynamic changes in SBP during puberty and DBP during postpuberty. Higher physical activity may reduce SBP levels in puberty independent of genetic susceptibility.