TY - JOUR
T1 - Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes
T2 - the consortium of childhood blood pressure
AU - Xie, Tian
AU - Ani, Alireza
AU - Vaez, Ahmad
AU - Nolte, Ilja M.
AU - Su, Shaoyong
AU - Ishikuro, Mami
AU - Wang, Siqi
AU - Zhang, Wenbo
AU - Soares, Ana Goncalves
AU - Motazedi, Ehsan
AU - Calas, Lucinda
AU - Ronkainen, Justiina
AU - Pedersen, Casper-Emil T.
AU - Lu, Xueling
AU - Stinson, Sara E.
AU - Felix, Janine F.
AU - Stankevic, Evelina
AU - Wang, Carol A.
AU - Thiering, Elisabeth
AU - Fernandez, Dietmar
AU - Calvo-Serra, Beatriz
AU - Stathopoulou, Maria G.
AU - Fore, Ruby
AU - Kumar, Ashish
AU - Tuhkanen, Johanna
AU - Bilbao, Jose Ramon
AU - Ibarluzea, Jesus
AU - Isaacs, Aaron
AU - Fonvig, Cilius Esmann
AU - Rivadeneira, Fernando
AU - Lund, Morten Asp Vonsild
AU - Holm, Louise Aas
AU - van der Most, Peter J.
AU - Riese, Harriette
AU - Narita, Akira
AU - Tamiya, Gen
AU - Flexeder, Claudia
AU - Wiersma, Rikstje
AU - Argoty-Pantoja, Anna D.
AU - Vinding, Rebecca
AU - Hansen, Tine Willum
AU - Kumler, Thomas
AU - Estarlich, Marisa
AU - Bustamante, Mariona
AU - Yuan, Wen Lun
AU - Boland-Auge, Anne
AU - Deleuze, Jean-Francois
AU - Petrelis, Alexandros M.
AU - Rifas-Shiman, Sheryl
AU - Kajantie, Eero
AU - Et al.
PY - 2026/9/1
Y1 - 2026/9/1
N2 - 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.
AB - 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.
KW - Childhood blood pressure
KW - Childhood heart rate
KW - Genome-wide association study
KW - Adult health outcomes
KW - GENOME-WIDE ASSOCIATION
KW - VARIANTS
KW - TRAJECTORIES
KW - METAANALYSIS
KW - CHILDREN
KW - DISEASE
KW - STRESS
U2 - 10.1093/eurheartj/ehag313
DO - 10.1093/eurheartj/ehag313
M3 - Article
SN - 0195-668X
VL - 47
SP - 4621
EP - 4637
JO - European Heart Journal
JF - European Heart Journal
IS - 33
ER -