Citation
Bradfield, Jonathan P.; Kember, Rachel L.; Ulrich, Anna; Balkiyarova, Zhanna; Alyass, Akram; Aris, Izzuddin M.; Bell, Joshua A.; Broadaway, K. Alaine; Chen, Zhanghua; & Chai, Jin-Fang, et al. (2024). Trans-Ancestral Genome-Wide Association Study of Longitudinal Pubertal Height Growth and Shared Heritability with Adult Health Outcomes. Genome Biology, 25(1), 22. PMCID: PMC10790528Abstract
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.
URL
http://dx.doi.org/10.1186/s13059-023-03136-zReference Type
Journal ArticleYear Published
2024Journal Title
Genome BiologyAuthor(s)
Bradfield, Jonathan P.Kember, Rachel L.
Ulrich, Anna
Balkiyarova, Zhanna
Alyass, Akram
Aris, Izzuddin M.
Bell, Joshua A.
Broadaway, K. Alaine
Chen, Zhanghua
Chai, Jin-Fang
Davies, Neil M.
Fernandez-Orth, Dietmar
Bustamante, Mariona
Fore, Ruby
Ganguli, Amitavo
Heiskala, Anni
Hottenga, Jouke-Jan
Íñiguez, Carmen
Kobes, Sayuko
Leinonen, Jaakko
Lowry, Estelle
Lyytikainen, Leo-Pekka
Mahajan, Anubha
Pitkänen, Niina
Schnurr, Theresia M.
Have, Christian Theil
Strachan, David P.
Thiering, Elisabeth
Vogelezang, Suzanne
Wade, Kaitlin H.
Wang, Carol A.
Wong, Andrew
Holm, Louise A.
Chesi, Alessandra
Choong, Catherine
Cruz, Miguel
Elliott, Paul
Franks, Steve
Frithioff-Bøjsøe, Christine
Gauderman, W. James
Glessner, Joseph T.
Gilsanz, Vicente
Griesman, Kendra
Hanson, Robert L.
Kaakinen, Marika
Kalkwarf, Heidi
Kelly, Andrea
Kindler, Joseph
Kähönen, Mika
Lanca, Carla
Lappe, Joan
Lee, Nanette R.
McCormack, Shana
Mentch, Frank D.
Mitchell, Jonathan A.
Mononen, Nina
Niinikoski, Harri
Oken, Emily
Pahkala, Katja
Sim, Xueling
Teo, Yik-Ying
Baier, Leslie J.
van Beijsterveldt, Toos
Adair, Linda S.
Boomsma, Dorret I.
de Geus, Eco J. C.
Guxens, Mònica
Eriksson, Johan G.
Felix, Janine F.
Gilliland, Frank D.
Hansen, Torben
Hardy, Rebecca
Hivert, Marie-France
Holm, Jens-Christian
Jaddoe, Vincent W. V.
Järvelin, Marjo-Riitta
Lehtimäki, Terho
Mackey, David A.
Meyre, David
Mohlke, Karen L.
Mykkänen, Juha
Oberfield, Sharon
Pennell, Craig E.
Perry, John R. B.
Raitakari, Olli T.
Rivadeneira, Fernando
Saw, Seang-Mei
Sebert, Sylvain
Shepherd, John A.
Standl, Marie
Sørensen, Thorkild I. A.
Timpson, Nicholas J.
Torrent, Maties
Willemsen, Gonneke
Hypponen, Elina
Power, Chris
Early Growth Genetics Consortium
McCarthy, Mark I
Freathy, Rachel M
Widén, Elisabeth
Hakonarson, Hakon
Prokopenko, Inga
Voight, Benjamin F
Zemel, Babette S
Grant, Struan F A
Cousminer, Diana L