Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Jonathan P. Bradfeld; Anna Ulrich; Rachel L Kember; Zhanna Balkhiyarova; Akram Alyass; Marika Kaakinen; Izzuddin M Aris; Inga Prokopenko; Joshua A Bell; Alaine Broadaway; Zhanghua Chen; Jin-Fang Chai; Neil M Davies; Dietmar Fernandez-Orth; Mariona Bustamante; Ruby Fore; Amitavo Ganguli; Anni Heiskala; Leo-Pekka Lyytikainen; Jaakko Leinonen; Estelle Lowry; Sayuko Kobes; Anubha Mahajan; Jouke-Jan Hottenga; Niina Pitkanen; Carmen Íñiguez; Theresia M Schnurr; Christian T Have; David P Strachan; Elisabeth Thiering; Suzanne Vogelezang; Kaitlin H. Wade; Carol A. Wang; Andrew Wong; Louise Aas Holm; Alessandra Chesi; Catherine Choong; Miguel Cruz; Paul Elliott; Steve Franks; Christine Frithiof-Bojsoe; W.J Gauderman; Joseph T Glessner; Vicente Gilsanz; Kendra Griesman; Robert L Hanson; Heidi Kalkwarf; Andrea Kelly; Joseph Kindler; Mika Kähönen; Carla Lanca; Joan Lappe; Nanette R Lee; Shana McCormack; Frank D Mentch; Jonathan A Mitchell; Nina Mononen; Harri Niinikoski; Emily Oken; Katja Pahkala; Xueling Sim; Yik-Ying Teo; Leslie J Baier; Toos van Beijsterveldt; Linda S Adair; Dorret I. Boomsma; Eco de Geus; Mònica Guxens; Johan G Eriksson; Janine F. Felix; Frank D Gilliland; Torben Hansen; Rebecca Hardy; Marie-France Hivert; Jens-Christian Holm; Vincent W.V Jaddoe; Marjo-Riitta Jarvelin; Terho Lehtimäki; David A Mackey; David Meyre; Karen L Mohlke; Juha Mykkänen; Sharon Oberfeld; Craig E. Pennell; John R. B. Perry; Olli T Raitakari; Fernando Rivadeneira; Seang-Mei Saw; Sylvain Sebert; John A Shepherd; Marie Standl; Thorkild I. A. Sorensen; Nicholas J. Timpson; Maties Torrent; Gonneke Willemsen; Elina Hypponen; Chris Power; MI McCarthy; Rachel M. Freathy; Elisabeth Widen; Hakon Hakonarson; Benjamin F Voight; Babette S Zemel; Struan F A Grant; Diana L. Cousminer

doi:10.1186/s13059-024-03276-w

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Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

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Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Jonathan P. Bradfeld, Anna Ulrich, Rachel L Kember, Zhanna Balkhiyarova, Akram Alyass, Marika Kaakinen, Izzuddin M Aris, Inga Prokopenko, Joshua A Bell, Alaine Broadaway, …

Genome biology, Vol.25(1), pp.22-41

21/05/2024

DOI: https://doi.org/10.1186/s13059-024-03276-w

PMID: 38773652

Abstract

Biotechnology & Applied Microbiology

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

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Title: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
Creators: Jonathan P. Bradfeld (Author) - Children's Hospital of Philadelphia
Anna Ulrich (Author) - University of Surrey, School of Biosciences
Rachel L Kember (Author) - University of Pennsylvania
Zhanna Balkhiyarova (Author) - University of Surrey, School of Biosciences
Akram Alyass - McMaster University
Marika Kaakinen - University of Surrey
Izzuddin M Aris - Harvard Pilgrim Health Care
Inga Prokopenko (Author) - University of Surrey, School of Biosciences
Joshua A Bell - MRC Epidemiology Unit
Alaine Broadaway - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Zhanghua Chen - University of Southern California
Jin-Fang Chai - National University of Singapore
Neil M Davies - MRC Epidemiology Unit
Dietmar Fernandez-Orth - Barcelona Institute for Global Health
Mariona Bustamante - Barcelona Institute for Global Health
Ruby Fore - Harvard Pilgrim Health Care
Amitavo Ganguli - Children's Hospital of Philadelphia
Anni Heiskala - University of Oulu
Leo-Pekka Lyytikainen - Tampere University
Jaakko Leinonen - Institute for Molecular Medicine Finland
Estelle Lowry - University of Oulu
Sayuko Kobes - NIDDK, Phoenix Epidemiol & Clin Res Ctr, NIH, Bethesda, MD USA
Anubha Mahajan - University of Oxford
Jouke-Jan Hottenga - University of Amsterdam
Niina Pitkanen - University of Turku
Carmen Íñiguez - Universitat de València
Theresia M Schnurr - University of Copenhagen
Christian T Have - University of Copenhagen
David P Strachan - St George's, University of London
Elisabeth Thiering - Helmholtz Zentrum München
Suzanne Vogelezang - Erasmus MC
Kaitlin H. Wade - University of Bristol
Carol A. Wang - University of Newcastle Australia
Andrew Wong - MRC Unit for Lifelong Health and Ageing
Louise Aas Holm - Novo Nordisk Foundation
Alessandra Chesi - Children's Hospital of Philadelphia
Catherine Choong - University of Western Australia
Miguel Cruz - Centro Medico Nacional Siglo XXI
Paul Elliott - Imperial College London
Steve Franks - Imperial College London
Christine Frithiof-Bojsoe - University of Copenhagen
W.J Gauderman - University of Southern California
Joseph T Glessner - Children's Hospital of Philadelphia
Vicente Gilsanz - Children's Hospital of Los Angeles
Kendra Griesman - Haverford College
Robert L Hanson
Heidi Kalkwarf - Cincinnati Children's Hospital Medical Center
Andrea Kelly - University of Pennsylvania
Joseph Kindler - University of Georgia
Mika Kähönen - Tampere University
Carla Lanca - Singapore National Eye Center
Joan Lappe - Creighton University
Nanette R Lee - University of San Carlos
Shana McCormack - University of Pennsylvania
Frank D Mentch - Children's Hospital of Philadelphia
Jonathan A Mitchell - University of Pennsylvania
Nina Mononen - Tampere University
Harri Niinikoski - University of Turku
Emily Oken - Supreme Council Of Health
Katja Pahkala - University of Turku
Xueling Sim - Duke-NUS Medical School
Yik-Ying Teo - Supreme Council Of Health
Leslie J Baier - NIDDK, Phoenix Epidemiol & Clin Res Ctr, NIH, Bethesda, MD USA
Toos van Beijsterveldt - University of Amsterdam
Linda S Adair - University of North Carolina at Chapel Hill
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Eco de Geus - University of Amsterdam
Mònica Guxens - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Johan G Eriksson - University of Helsinki
Janine F. Felix - Erasmus MC
Frank D Gilliland - Univ Southern Calif, Dept Populat & Publ Hlth Sci, Los Angeles, CA 90032 USA
Torben Hansen - University of Copenhagen
Rebecca Hardy - Cohort
Marie-France Hivert - Supreme Council Of Health
Jens-Christian Holm - University of Copenhagen
Vincent W.V Jaddoe - Erasmus MC
Marjo-Riitta Jarvelin - Supreme Council Of Health
Terho Lehtimäki - Tampere University
David A Mackey - Lions Eye Institute
David Meyre - McMaster University
Karen L Mohlke - University of North Carolina at Chapel Hill
Juha Mykkänen - Turku University Hospital
Sharon Oberfeld - Columbia University Irving Medical Center
Craig E. Pennell - University of Newcastle Australia
John R. B. Perry - University of Cambridge
Olli T Raitakari - Turku University Hospital
Fernando Rivadeneira - Erasmus MC
Seang-Mei Saw - Natl Univ Hlth Syst, Singapore, Singapore
Sylvain Sebert - University of Oulu
John A Shepherd - University of Hawaiʻi at Mānoa
Marie Standl - Helmholtz Zentrum München
Thorkild I. A. Sorensen - University of Copenhagen
Nicholas J. Timpson - University of Bristol
Maties Torrent - Health Research Institute of the Balearic Islands
Gonneke Willemsen - Vrije Universiteit Amsterdam
Elina Hypponen - UCL Australia
Chris Power - Great Ormond Street Hospital
MI McCarthy - Wellcome Centre for Human Genetics
Rachel M. Freathy - University of Exeter
Elisabeth Widen - Institute for Molecular Medicine Finland
Hakon Hakonarson - University of Pennsylvania
Benjamin F Voight - University of Pennsylvania
Babette S Zemel - University of Pennsylvania
Struan F A Grant - University of Pennsylvania
Diana L. Cousminer - University of Pennsylvania
Publication Details: Genome biology, Vol.25(1), pp.22-41
Publisher: Springer Nature
Date published: 21/05/2024
Grants: 20/0006307, Diabetes UK (United Kingdom, London)
Longitools, H2020-SCI-2019-874739, Horizon 2020
Identifiers: 99911166402346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

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