ArticleGenome biology2024
Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.
Erratum issuedOpen access · goldAbstract read
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Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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12citing papers in PubMed
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- FEMA-Long: Modeling unstructured covariances for discovery of time-dependent effects in large-scale longitudinal datasets.PLoS genetics · 2026Article
- Disentangling the relationship between intrauterine exposures and offspring growth in mid-childhood.BMC medicine · 2026Article
- Distinct genetic profiles influence body mass index between infancy and adolescence.Nature communications · 2026Article
- Functional analysis of NPR2 variants supports the therapeutic rationale for CNP in short stature.American journal of human genetics · 2026Article
- The Impact of Nutrition, Genetics, Environment, and Common Issues on Adolescent Growth and Development.Advances in experimental medicine and biology · 2026Review
- Short stature-related factors and nomogram-based risk prediction in children aged 7-12: evidence from Chaozhou, China.Frontiers in endocrinology · 2026Article
- Early life growth is related to pubertal growth and adult height - a QEPS-model analysis.Pediatric research · 2025Article
- Effects of childhood and adult height on later life cardiovascular disease risk estimated through Mendelian randomization.European journal of epidemiology · 2025Article
- Development and validation of a polygenic risk score for height in a Greek cohort: Association with blood pressure measurements.Frontiers in genetics · 2025Article
- Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.Genome biology · 2024Article
- Mapping an intelligent algorithm for predicting female adolescents' cervical vertebrae maturation stage with high recall and accuracy.Progress in orthodontics · 2024Article
- Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians.Human molecular genetics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
107 authors at 20 institutions in 14 countries.
Jonathan P BradfieldCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Rachel L KemberDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Anna UlrichDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford, UK.
Zhanna BalkhiyarovaDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford, UK.
Akram AlyassDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Izzuddin M ArisDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
Joshua A BellMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
K Alaine BroadawayDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Zhanghua ChenDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, 90032, USA.
Jin-Fang ChaiSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Neil M DaviesMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Dietmar Fernandez-OrthISGlobal, Barcelona, Spain.
Mariona BustamanteISGlobal, Barcelona, Spain.
Ruby ForeDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
Amitavo GanguliCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Anni HeiskalaCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
Jouke-Jan HottengaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Carmen ÍñiguezDepartment of Statistics and Computational Research, Universitat de València, Valencia, Spain.
Sayuko KobesPhoenix Epidemiology and Clinical Research Center, NIDDK, NIH, Bethesda, USA.
Jaakko LeinonenInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Estelle LowryCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
Leo-Pekka LyytikainenDepartment of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33014, Tampere, Finland.
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Niina PitkänenResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Theresia M SchnurrFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Christian Theil HaveFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
David P StrachanPopulation Health Research Institute, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
Elisabeth ThieringInstitute of Epidemiology, Helmholtz Zentrum München- German Research Center for Environmental Health, Neuherberg, Germany.
Suzanne VogelezangThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Kaitlin H WadeMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Carol A WangSchool of Medicine and Public Health, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW, 2308, Australia.
Andrew WongMRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Louise Aas HolmFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Alessandra ChesiDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Catherine ChoongFaculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia.
Miguel CruzUnidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Paul ElliottMRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK.
Steve FranksInstitute of Reproductive & Developmental Biology, Imperial College London, London, UK.
Christine Frithioff-BøjsøeFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
W James GaudermanDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, 90032, USA.
Joseph T GlessnerCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Vicente GilsanzCenter for Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Kendra GriesmanHaverford College, Haverford, PA, USA.
Robert L HansonPhoenix Epidemiology and Clinical Research Center, NIDDK, NIH, Bethesda, USA.
Marika KaakinenDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford, UK.
Heidi KalkwarfDepartment of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, USA.
Andrea KellyDepartment of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Joseph KindlerCollege of Family and Consumer Sciences, University of Georgia, Athens, GA, USA.
Mika KähönenDepartment of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, 33014, Tampere, Finland.
Carla LancaSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Joan LappeDepartment of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA.
Nanette R LeeUSC-Office of Population Studies Foundation, Inc, University of San Carlos, Cebu, Philippines.
Shana McCormackDepartment of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Frank D MentchCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Jonathan A MitchellDepartment of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Nina MononenDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center - Tampere, Tampere University, 33014, Tampere, Finland.
Harri NiinikoskiDepartment of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
Emily OkenDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
Katja PahkalaResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Xueling SimSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Yik-Ying TeoSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Leslie J BaierPhoenix Epidemiology and Clinical Research Center, NIDDK, NIH, Bethesda, USA.
Toos van BeijsterveldtDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Linda S AdairDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Eco de GeusDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Mònica GuxensISGlobal, Barcelona, Spain.
Johan G ErikssonInstitute of Clinical Medicine Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
Janine F FelixThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Frank D GillilandDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, 90032, USA.
Penn Medicine Biobank
Torben HansenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Rebecca HardyCohort and Longitudinal Studies Enhancement Resources (CLOSER), UCL Institute of Education, London, UK.
Marie-France HivertDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
Jens-Christian HolmFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Vincent W V JaddoeThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Marjo-Riitta JärvelinCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center - Tampere, Tampere University, 33014, Tampere, Finland.
David A MackeyLions Eye Institute, Centre for Ophthalmology and Visual Science, Centre for Eye Research Australia, University of Western Australia, Perth, WA, Australia.
David MeyreDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Juha MykkänenResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Sharon OberfieldDivision of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA.
Craig E PennellSchool of Medicine and Public Health, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW, 2308, Australia.
John R B PerryMetabolic Research Laboratory, School of Clinical Medicine, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Olli RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Fernando RivadeneiraDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Seang-Mei SawSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Sylvain SebertCenter for Life Course Health Research, University of Oulu, Oulu, Finland.
John A ShepherdDepartment of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA.
Marie StandlInstitute of Epidemiology, Helmholtz Zentrum München- German Research Center for Environmental Health, Neuherberg, Germany.
Thorkild I A SørensenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Nicholas J TimpsonMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Maties TorrentCIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Gonneke WillemsenDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Elina HypponenUCL Great Ormond Street Institute of Child Health, London, UK.
Chris PowerUCL Great Ormond Street Institute of Child Health, London, UK.
Early Growth Genetics Consortium
Mark I McCarthyWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Rachel M FreathyDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, EX2 5DW, UK.
Elisabeth WidénInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Inga ProkopenkoDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford, UK.
Benjamin F VoightDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Babette S ZemelDepartment of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Struan F A GrantCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. grants@email.chop.edu.
Diana L CousminerCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. diana.l.cousminer@gsk.com.ORCID 0000-0001-8864-7893
Children's Hospital of Philadelphia · USUniversity of Copenhagen · DKUniversity of Turku · FIVrije Universiteit Amsterdam · NLErasmus MC · NLHarvard University · USNational University of Singapore · SGTampere University · FIUniversity of Bristol · GBUniversity of Helsinki · FIUniversity of North Carolina at Chapel Hill · USUniversity of Southern California · USUniversity of Surrey · GBBarcelona Institute for Global Health · ESCentre for Human Genetics · GBHelmholtz Zentrum München · DEImperial College London · GBUniversity of Oulu · FICentre National de la Recherche Scientifique · FRChildren's Hospital of Los Angeles · US
Funding
Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1MInstitutional Career Development CoreKL2TR002381 · NCATS · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Anandi Nayan Sheth · 2017 to 2026
$14.1MNeuro HPA Project 1U54AG062334 · NIA · EMORY UNIVERSITY · PI Ighovwerha Ofotokun · 2018 to 2026
$12.2MGenome Wide Association Study for Childhood ObesityR01HD056465 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A · 2008 to 2024
$9.5MFunctional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8MGenetic Epidemiology of Diabetes and ObesityZIADK069028 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HANSON, ROBERT · 2009 to 2025
$7.5MThe Genetic Epidemiology of Heart, Lung, and Blood TraitsTraining Grant (GenHLB)T32HL129982 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christy Leigh Avery, KAREN L. MOHLKE · 2016 to 2026
$3.8MGenomics of bone and body composition traits in childrenR01HD100406 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A, ZEMEL, BABETTE S · 2020 to 2024
$3.4MIntegrating genomic studies of gestational duration and birth weight to understand maternal and fetal causes of adverse pregnancy outcomes and links with later diseasesR01HD101669 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI FREATHY, RACHEL, JACOBSSON, BO · 2021 to 2024
$2.1MAlgorithms to identify non-coding mutational burden and disease-relevant pathwaysR56DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2019 to 2019
$272kDiabetes UK 20/0006307Medical Research Council G0802782Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MC_UU_00006/2Medical Research Council MC_UU_12015/2Medical Research Council MC_UU_12019/2MRF MC_UU_00006/2MRF MC_UU_12015/2NCATS NIH HHS KL2 TR002381NCATS NIH HHS UL1 TR002378NHLBI NIH HHS T32 HL129982NIA NIH HHS U54 AG062334NICHD NIH HHS R01 HD056465NICHD NIH HHS R01 HD100406NICHD NIH HHS R01 HD101669NIDDK NIH HHS R56 DK101478NIDDK NIH HHS UM1 DK126194NIH HHS R01 HD056465NIH HHS T32HL129982Wellcome TrustWellcome Trust 212259/Z/18/ZWellcome Trust WT220390
Abstract
backgroundPubertal 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.
resultsLarge-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.
conclusionWe 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.
Indexed as
Diabetes Mellitus, Type 2Genome-Wide Association StudyAdolescentAdultBody HeightChildChild, PreschoolHumansLongitudinal StudiesOutcome Assessment, Health CarePhenotypePuberty
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