Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.
BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.