Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study

Abstract

Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for approximately 37 years. The multi-ancestry genome-wide polygenic risk scores (PRSs) for systolic BP (SBP), diastolic BP (DBP), and hypertension were tested for an association with incident hypertension and stage 2 hypertension using Cox proportional hazards models. Race-stratified analyses were adjusted for baseline age, age2, sex, body mass index, genetic principal components, and BP. In Black participants, each standard deviation increase in SBP and DBP PRS conferred a 38% (p = 0.009) and 22% (p = 0.02) increased risk of hypertension and a 74% (p < 0.001) and 50% (p < 0.001) increased risk of stage 2 hypertension, respectively, while no association was observed with the hypertension PRSs. In Whites, each standard deviation increase in SBP, DBP, and hypertension PRS conferred a 24% (p < 0.05), 29% (p = 0.01), and 25% (p < 0.001) increased risk of hypertension, and a 27% (p = 0.08), 29% (0.01), and 42% (p < 0.001) increased risk of stage 2 hypertension, respectively. The addition of BP PRSs to the covariable-only models generally improved the C-statistics (p < 0.05). Multi-ancestry BP PRSs demonstrate the utility of genomic information in the early life prediction of hypertension.

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment

“…Furthermore, the addition of the PRS to a model including childhood age, sex, body mass index, and measured blood pressure increased its predictive value based on the difference in C statistics. 20 In total, these findings reveal unique opportunities for “targeted” primordial prevention, possibly enabling aggressive early life interventions, such as dietary recommendations or physical activity intervention, in genetically susceptible individuals before clinical manifestation of CVD risk factors and downstream clinical CVD events.…”

“…Indeed, early work from studies that have longitudinally followed participants from childhood through midlife, including data from the Young Finns Study and BHS (Bogalusa Heart Study), have already provided compelling evidence for the relevance of PRS in identifying children at increased risk of developing obesity, 19,126 diabetes, 22,125 and hypertension. 20 For example, Sun et al 20 Note: (1) Data are manually curated based on PGS Catalog and individual literatures. (2) For PGS developed from source GWAS with >1 ancestry groups, only the 2 largest ancestry groups will be displayed.…”

“…Indeed, early work from studies that have longitudinally followed participants from childhood through midlife, including data from the Young Finns Study and BHS (Bogalusa Heart Study), have already provided compelling evidence for the relevance of PRS in identifying children at increased risk of developing obesity, 19,126 diabetes, 22,125 and hypertension. 20 For example, Sun et al 20 found that non-Hispanic Black BHS participants in the highest quartile of a multiethnic blood pressure PRS had more than a 2-fold increased risk of developing severe hypertension from childhood through midlife compared to those in the first quartile, even after adjusting for measured blood pressure at the first childhood study visit. Furthermore, the addition of the PRS to a model including childhood age, sex, body mass index, and measured blood pressure increased its predictive value based on the difference in C statistics.…”

“…For example, early works from the Bogalusa Heart and Young Finns Studies have demonstrated that genetically estimated CVD risk factors can improve the prediction of adverse cardiometabolic profiles in midlife when added to models already including those same clinically measured CVD risk factors in childhood. 19–23 These data clearly implicate genomic susceptibility as an early determinant of CVD, while alluding to its translational potential for improving cardiovascular health across the life-course.…”

Assessment of polygenic risk of hypertension

“…О перспективности применения ШГР для оценки риска развития АГ свидетельствуют результаты недавно проведенного исследования [26], в которое вошли данные проспективного наблюдения (в течение 37 лет). Авторы использовали ранее разработанные на многоэтнических когортах ШГР для САД, ДАД, и АГ, которые включали 24807, 149559 и 234228 ВНП, соответственно [27].…”