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

doi:10.1093/eurheartj/ehag313

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^*

^*Corresponding author voor dit werk

Onderzoeksoutput › Academic › peer review

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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.

Originele taal-2	English
Tijdschrift	European Heart Journal
DOI's	https://doi.org/10.1093/eurheartj/ehag313
Status	E-pub ahead of print - 27-apr-2026

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10.1093/eurheartj/ehag313Licentie: CC BY

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Xie, T., Ani, A., Vaez, A., Nolte, I. M., Su, S., Ishikuro, M., Wang, S., Zhang, W., Soares, A. G., Motazedi, E., Calas, L., Ronkainen, J., Pedersen, C.-E. T., Lu, X., Stinson, S. E., Felix, J. F., Stankevic, E., Wang, C. A., Thiering, E., ... Snieder, H. (2026). Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure. European Heart Journal. Online publicatie vooraf. https://doi.org/10.1093/eurheartj/ehag313

@article{61cf3231b4244a98be4f570e7d7e5f0c,

title = "Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure",

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.",

author = "Tian Xie and Alireza Ani and Ahmad Vaez and Nolte, \{Ilja M\} and Shaoyong Su and Mami Ishikuro and Siqi Wang and Wenbo Zhang and Soares, \{Ana Goncalves\} and Ehsan Motazedi and Lucinda Calas and Justiina Ronkainen and Pedersen, \{Casper-Emil T\} and Xueling Lu and Stinson, \{Sara E\} and Felix, \{Janine F\} and Evelina Stankevic and Wang, \{Carol A\} and Elisabeth Thiering and Dietmar Fern{\'a}ndez and Beatriz Calvo-Serra and Stathopoulou, \{Maria G\} and Ruby Fore and Ashish Kumar and Johanna Tuhkanen and Bilbao, \{Jose Ramon\} and Jesus Ibarluzea and Aaron Isaacs and Fonvig, \{Cilius Esmann\} and Fernando Rivadeneira and Lund, \{Morten Asp Vonsild\} and Holm, \{Louise Aas\} and \{van der Most\}, \{Peter J\} and Harri{\"e}tte Riese and Akira Narita and Gen Tamiya and Claudia Flexeder and Rikstje Wiersma and Argoty-Pantoja, \{Anna D\} and Rebecca Vinding and Hansen, \{Tine Willum\} and Thomas K{\"u}mler and Marisa Estarlich and Mariona Bustamante and Yuan, \{Wen Lun\} and Anne Boland-Aug{\'e} and Jean-Fran{\c c}ois Deleuze and Petrelis, \{Alexandros M\} and Sheryl Rifas-Shiman and Eero Kajantie and Nora Fernandez-Jimenez and Loreto Santa-Marina and Arts, \{Ilja C W\} and Jari Lahti and Timo Strandberg and Inger Kull and Anna Bergstr{\"o}m and Marie-France Hivert and Klaus B{\o}nnelykke and Shinichi Kuriyama and Beilin, \{Lawrence J\} and Mori, \{Trevor A\} and Hartman, \{Catharina A\} and Niels Grarup and Carel Thijs and Katri R{\"a}ikk{\"o}nen and Erik Mel{\'e}n and Emily Oken and Sophie Visvikis-Siest and G{\"u}tzkow, \{Kristine B\} and Regina Grazuleviciene and Barbara Heude and Leda Chatzi and Martine Vrijheid and Marie Standl and Tanja Vrijkotte and Pennell, \{Craig E\} and Oldehinkel, \{Albertine J\} and Torben Hansen and Jaddoe, \{Vincent W V\} and Jens-Christian Holm and Sylvain Sebert and Timpson, \{Nicholas J\} and Taku Obara and Xiaoling Wang and Lawlor, \{Deborah A\} and Eva Corpeleijn and Ahluwalia, \{Tarunveer S\} and Harold Snieder",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2026",

month = apr,

day = "27",

doi = "10.1093/eurheartj/ehag313",

language = "English",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

}

Xie, T , Ani, A , Vaez, A , Nolte, IM, Su, S, Ishikuro, M, Wang, S , Zhang, W, Soares, AG, Motazedi, E, Calas, L, Ronkainen, J, Pedersen, C-ET, Lu, X, Stinson, SE, Felix, JF, Stankevic, E, Wang, CA, Thiering, E, Fernández, D, Calvo-Serra, B, Stathopoulou, MG, Fore, R, Kumar, A, Tuhkanen, J, Bilbao, JR, Ibarluzea, J, Isaacs, A, Fonvig, CE, Rivadeneira, F, Lund, MAV, Holm, LA, van der Most, PJ , Riese, H, Narita, A, Tamiya, G, Flexeder, C, Wiersma, R , Argoty-Pantoja, AD, Vinding, R, Hansen, TW, Kümler, T, Estarlich, M, Bustamante, M, Yuan, WL, Boland-Augé, A, Deleuze, J-F, Petrelis, AM, Rifas-Shiman, S, Kajantie, E, Fernandez-Jimenez, N, Santa-Marina, L, Arts, ICW, Lahti, J, Strandberg, T, Kull, I, Bergström, A, Hivert, M-F, Bønnelykke, K, Kuriyama, S, Beilin, LJ, Mori, TA, Hartman, CA, Grarup, N, Thijs, C, Räikkönen, K, Melén, E, Oken, E, Visvikis-Siest, S, Gützkow, KB, Grazuleviciene, R, Heude, B, Chatzi, L, Vrijheid, M, Standl, M, Vrijkotte, T, Pennell, CE, Oldehinkel, AJ, Hansen, T, Jaddoe, VWV, Holm, J-C, Sebert, S, Timpson, NJ, Obara, T, Wang, X, Lawlor, DA, Corpeleijn, E, Ahluwalia, TS & Snieder, H 2026, 'Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure', European Heart Journal. https://doi.org/10.1093/eurheartj/ehag313

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 - Fernández, 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, Harriëtte

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 - Kümler, Thomas

AU - Estarlich, Marisa

AU - Bustamante, Mariona

AU - Yuan, Wen Lun

AU - Boland-Augé, Anne

AU - Deleuze, Jean-François

AU - Petrelis, Alexandros M

AU - Rifas-Shiman, Sheryl

AU - Kajantie, Eero

AU - Fernandez-Jimenez, Nora

AU - Santa-Marina, Loreto

AU - Arts, Ilja C W

AU - Lahti, Jari

AU - Strandberg, Timo

AU - Kull, Inger

AU - Bergström, Anna

AU - Hivert, Marie-France

AU - Bønnelykke, Klaus

AU - Kuriyama, Shinichi

AU - Beilin, Lawrence J

AU - Mori, Trevor A

AU - Hartman, Catharina A

AU - Grarup, Niels

AU - Thijs, Carel

AU - Räikkönen, Katri

AU - Melén, Erik

AU - Oken, Emily

AU - Visvikis-Siest, Sophie

AU - Gützkow, Kristine B

AU - Grazuleviciene, Regina

AU - Heude, Barbara

AU - Chatzi, Leda

AU - Vrijheid, Martine

AU - Standl, Marie

AU - Vrijkotte, Tanja

AU - Pennell, Craig E

AU - Oldehinkel, Albertine J

AU - Hansen, Torben

AU - Jaddoe, Vincent W V

AU - Holm, Jens-Christian

AU - Sebert, Sylvain

AU - Timpson, Nicholas J

AU - Obara, Taku

AU - Wang, Xiaoling

AU - Lawlor, Deborah A

AU - Corpeleijn, Eva

AU - Ahluwalia, Tarunveer S

AU - Snieder, Harold

PY - 2026/4/27

Y1 - 2026/4/27

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.

U2 - 10.1093/eurheartj/ehag313

DO - 10.1093/eurheartj/ehag313

M3 - Article

C2 - 42036355

SN - 0195-668X

JO - European Heart Journal

JF - European Heart Journal

ER -

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

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