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Bradfield, J.P.* ; Kember, R.L.* ; Ulrich, A.* ; Balkiyarova, Z.* ; Alyass, A.* ; Aris, I.M.* ; Bell, J.A.* ; Broadaway, K.A.* ; Chen, Z.* ; Chai, J.F.* ; Davies, N.M.* ; Fernandez-Orth, D.* ; Bustamante, M.* ; Fore, R.* ; Ganguli, A.* ; Heiskala, A.* ; Hottenga, J.J.* ; Iñiguez, C.* ; Kobes, S.* ; Leinonen, J.T.* ; Lowry, E.* ; Lyytikäinen, L.P.* ; Mahajan, A.* ; Pitkänen, N.* ; Schnurr, T.M.* ; Have, C.T.* ; Strachan, D.P.* ; Thiering, E. ; Vogelezang, S.* ; Wade, K.H.* ; Wang, C.A.* ; Wong, A.* ; Holm, L.A.* ; Chesi, A.* ; Choong, C.* ; Cruz, M.* ; Elliott, P.* ; Franks, S.* ; Frithioff-Bøjsøe, C.* ; Gauderman, W.J.* ; Glessner, J.T.* ; Gilsanz, V.* ; Griesman, K.* ; Hanson, R.L.* ; Kaakinen, M.* ; Kalkwarf, H.* ; Kelly, A.* ; Kindler, J.* ; Kähönen, M.* ; Lanca, C.* ; Lappe, J.* ; Lee, N.R.* ; McCormack, S.E.* ; Mentch, F.D.* ; Mitchell, J.A.* ; Mononen, N.* ; Niinikoski, H.* ; Oken, E.* ; Pahkala, K.* ; Sim, X.* ; Teo, Y.Y.* ; Baier, L.J.* ; van Beijsterveldt, T.* ; Adair, L.S.* ; Boomsma, D.I.* ; de Geus, E.* ; Guxens, M.* ; Eriksson, J.G.* ; Felix, J.F.* ; Gilliland, F.D.* ; Hansen, T.* ; Hardy, R.* ; Hivert, M.F.* ; Holm, J.C.* ; Jaddoe, V.W.V.* ; Järvelin, M.R.* ; Lehtimäki, T.* ; Mackey, D.A.* ; Meyre, D.* ; Mohlke, K.L.* ; Mykkänen, J.* ; Oberfield, S.* ; Pennell, C.E.* ; Perry, J.R.B.* ; Raitakari, O.* ; Rivadeneira, F.* ; Saw, S.M.* ; Sebert, S.* ; Shepherd, J.A.* ; Standl, M. ; Sørensen, T.I.A.* ; Timpson, N.J.* ; Torrent, M.* ; Willemsen, G.* ; Hyppönen, E.* ; Power, C.* ; McCarthy, M.I.* ; Freathy, R.M.* ; Widén, E.* ; Hakonarson, H.* ; Prokopenko, I.* ; Voight, B.F.* ; Zemel, B.S.* ; Grant, S.F.A.* ; Cousminer, D.L.*

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

Genome Biol. 25:22 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Childhood Growth; Age; Birth; Sitar; Tempo; Adolescence; Regression; Mutations; Variants; Spectrum
ISSN (print) / ISBN 1474-760X
e-ISSN 1465-6906
Journal Genome Biology
Quellenangaben Volume: 25, Issue: 1, Pages: , Article Number: 22 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants
National Institutes of Health
Wellcome Trust
Academy of Finland
Medical Research Council
Wellcome Senior Research Fellowship
MRC (UK) Programme grant
Diabetes UK
European Union
Agence Nationale de la Recherche
European Union through the "Fonds europeen de developpement regional" (FEDER)
"Conseil Regional des Hauts-de-France" (Hauts-de-France Regional Council)
"Metropole Europeenne de Lille" (MEL, European Metropolis of Lille)
Daniel B. Burke Endowed Chair for Diabetes Research