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PubMed · 42036355

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

Tian Xie·Alireza Ani·Ahmad Vaez·Ilja M Nolte·Shaoyong Su·Mami Ishikuro·Siqi Wang·Wenbo Zhang·Ana Goncalves Soares·Ehsan Motazedi·Lucinda Calas·Justiina Ronkainen·Casper-Emil T Pedersen·Xueling Lu·Sara E Stinson·Janine F Felix·Evelina Stankevic·Carol A Wang·Elisabeth Thiering·Dietmar Fernández·Beatriz Calvo-Serra·Maria G Stathopoulou·Ruby Fore·Ashish Kumar·Johanna Tuhkanen·Jose Ramon Bilbao·Jesus Ibarluzea·Aaron Isaacs·Cilius Esmann Fonvig·Fernando Rivadeneira·Morten Asp Vonsild Lund·Louise Aas Holm·Peter J van der Most·Harriëtte Riese·Akira Narita·Gen Tamiya·Claudia Flexeder·Rikstje Wiersma·Anna D Argoty-Pantoja·Rebecca Vinding·Tine Willum Hansen·Thomas Kümler·Marisa Estarlich·Mariona Bustamante·Wen Lun Yuan·Anne Boland-Augé·Jean-François Deleuze·Alexandros M Petrelis·Sheryl Rifas-Shiman·Eero Kajantie·Nora Fernandez-Jimenez·Loreto Santa-Marina·Ilja C W Arts·Jari Lahti·Timo Strandberg·Inger Kull·Anna Bergström·Marie-France Hivert·Klaus Bønnelykke·Shinichi Kuriyama·Lawrence J Beilin·Trevor A Mori·Catharina A Hartman·Niels Grarup·Carel Thijs·Katri Räikkönen·Erik Melén·Emily Oken·Sophie Visvikis-Siest·Kristine B Gützkow·Regina Grazuleviciene·Barbara Heude·Leda Chatzi·Martine Vrijheid·Marie Standl·Tanja Vrijkotte·Craig E Pennell·Albertine J Oldehinkel·Torben Hansen·Vincent W V Jaddoe·Jens-Christian Holm·Sylvain Sebert·Nicholas J Timpson·Taku Obara·Xiaoling Wang·Deborah A Lawlor·Eva Corpeleijn·Tarunveer S Ahluwalia·Harold Snieder·Lifelines Cohort Study, ICBP Consortium

Abstract

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.

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BibTeXRIS

Tian Xie, Alireza Ani, Ahmad Vaez, Ilja M Nolte, Shaoyong Su, Mami Ishikuro, Siqi Wang, Wenbo Zhang, Ana Goncalves Soares, Ehsan Motazedi, Lucinda Calas, Justiina Ronkainen, Casper-Emil T Pedersen, Xueling Lu, Sara E Stinson, Janine F Felix, Evelina Stankevic, Carol A Wang, Elisabeth Thiering, Dietmar Fernández, Beatriz Calvo-Serra, Maria G Stathopoulou, Ruby Fore, Ashish Kumar, Johanna Tuhkanen, Jose Ramon Bilbao, Jesus Ibarluzea, Aaron Isaacs, Cilius Esmann Fonvig, Fernando Rivadeneira, Morten Asp Vonsild Lund, Louise Aas Holm, Peter J van der Most, Harriëtte Riese, Akira Narita, Gen Tamiya, Claudia Flexeder, Rikstje Wiersma, Anna D Argoty-Pantoja, Rebecca Vinding, Tine Willum Hansen, Thomas Kümler, Marisa Estarlich, Mariona Bustamante, Wen Lun Yuan, Anne Boland-Augé, Jean-François Deleuze, Alexandros M Petrelis, Sheryl Rifas-Shiman, Eero Kajantie, Nora Fernandez-Jimenez, Loreto Santa-Marina, Ilja C W Arts, Jari Lahti, Timo Strandberg, Inger Kull, Anna Bergström, Marie-France Hivert, Klaus Bønnelykke, Shinichi Kuriyama, Lawrence J Beilin, Trevor A Mori, Catharina A Hartman, Niels Grarup, Carel Thijs, Katri Räikkönen, Erik Melén, Emily Oken, Sophie Visvikis-Siest, Kristine B Gützkow, Regina Grazuleviciene, Barbara Heude, Leda Chatzi, Martine Vrijheid, Marie Standl, Tanja Vrijkotte, Craig E Pennell, Albertine J Oldehinkel, Torben Hansen, Vincent W V Jaddoe, Jens-Christian Holm, Sylvain Sebert, Nicholas J Timpson, Taku Obara, Xiaoling Wang, Deborah A Lawlor, Eva Corpeleijn, Tarunveer S Ahluwalia, Harold Snieder, Lifelines Cohort Study, ICBP Consortium. 2026-09-02. Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.. https://doi.org/10.1093/eurheartj%2Fehag313

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