RT Journal Article
T1 Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
A1 Bradfield, Jonathan P.
A1 Kember, Rachel L
A1 Ulrich, Anna
A1 Balkiyarova, Zhanna
A1 Alyass, Akram
A1 Aris, Izzuddin M
A1 Bell, Joshua A
A1 Broadaway, K Alaine
A1 Chen, Zhanghua
A1 Chai, Jin-Fang
A1 Davies, Neil M
A1 Fernandez-Orth, Dietmar
A1 Bustamante, Mariona
A1 Fore, Ruby
A1 Ganguli, Amitavo
A1 Heiskala, Anni
A1 Hottenga, Jouke-Jan
A1 Íñiguez, Carmen
A1 Kobes, Sayuko
A1 Leinonen, Jaakko
A1 Lowry, Estelle
A1 Lyytikainen, Leo-Pekka
A1 Mahajan, Anubha
A1 Pitkänen, Niina
A1 Schnurr, Theresia M.
A1 Have, Christian Theil
A1 Strachan, David P
A1 Thiering, Elisabeth
A1 Vogelezang, Suzanne
A1 Wade, Kaitlin H
A1 Wang, Carol A.
A1 Wong, Andrew
A1 Holm, Louise Aas
A1 Chesi, Alessandra
A1 Choong, Catherine
A1 Cruz, Miguel
A1 Elliott, Paul
A1 Franks, Steve
A1 Frithioff-Bøjsøe, Christine
A1 Gauderman, W James
A1 Glessner, Joseph T
A1 Gilsanz, Vicente
A1 Griesman, Kendra
A1 Hanson, Robert L
A1 Kaakinen, Marika
A1 Kalkwarf, Heidi
A1 Kelly, Andrea
A1 Kindler, Joseph
A1 Kähönen, Mika
A1 Lanca, Carla
A1 Lappe, Joan
A1 Lee, Nanette R
A1 McCormack, Shana
A1 Mentch, Frank D
A1 Mitchell, Jonathan A
A1 Mononen, Nina
A1 Niinikoski, Harri
A1 Oken, Emily
A1 Pahkala, Katja
A1 Sim, Xueling
A1 Teo, Yik-Ying
A1 Baier, Leslie J
A1 van Beijsterveldt, Toos
A1 Adair, Linda S.
A1 Boomsma, Dorret I.
A1 de Geus, Eco
A1 Guxens, Mònica
A1 Eriksson, Johan G.
A1 Felix, Janine F
A1 Gilliland, Frank D
A1 Biobank, Penn Medicine
A1 Hansen, Torben
A1 Hardy, Rebecca
A1 Hivert, Marie-France
A1 Holm, Jens-Christian
A1 Jaddoe, Vincent W V
A1 Järvelin, Marjo-Riitta
A1 Lehtimäki, Terho
A1 Mackey, David A
A1 Meyre, David
A1 Mohlke, Karen L
A1 Mykkänen, Juha
A1 Oberfield, Sharon
A1 Pennell, Craig E
A1 Perry, John R B
A1 Raitakari, Olli
A1 Rivadeneira, Fernando
A1 Saw, Seang-Mei
A1 Sebert, Sylvain
A1 Shepherd, John A
A1 Standl, Marie
A1 Sørensen, Thorkild I A
A1 Timpson, Nicholas J.
A1 Torrent Quetglas, Maties
A1 Willemsen, Gonneke
A1 Hypponen, Elina
A1 Power, Chris
A1 McCarthy, Mark I
A1 Freathy, Rachel M
A1 Widen, Elisabeth
A1 Hakonarson, Hakon
A1 Prokopenko, Inga
A1 Voight, Benjamin F
A1 Zemel, Babette S
A1 Grant, Struan F A
A1 Cousminer, Diana L.
AB 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.
PB BMC
YR 2024
FD 2024-01-16
LK https://hdl.handle.net/20.500.13003/20162
UL https://hdl.handle.net/20.500.13003/20162
LA eng
NO Bradfield JP, Kember RL, Ulrich A, Balkiyarova Z, Alyass A, Aris IM, et al. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes. Genome Biol. 2024 Jan 16;25(1):22.
DS Docusalut
RD 20 jun. 2026