@article{20.500.13003/20162,
year = {2024},
month = {1},
url = {https://hdl.handle.net/20.500.13003/20162},
abstract = {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.},
publisher = {BMC},
title = {Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes},
doi = {10.1186/s13059-023-03136-z},
journal = {Genome Biology},
author = {Bradfield, Jonathan P.
 and Kember, Rachel L and Ulrich, Anna and Balkiyarova, Zhanna and Alyass, Akram and Aris, Izzuddin M and Bell, Joshua A and Broadaway, K Alaine and Chen, Zhanghua and Chai, Jin-Fang and Davies, Neil M and Fernandez-Orth, Dietmar and Bustamante, Mariona and Fore, Ruby and Ganguli, Amitavo and Heiskala, Anni and Hottenga, Jouke-Jan and Íñiguez, Carmen and Kobes, Sayuko and Leinonen, Jaakko and Lowry, Estelle and Lyytikainen, Leo-Pekka and Mahajan, Anubha and Pitkänen, Niina and Schnurr, Theresia M. and Have, Christian Theil and Strachan, David P and Thiering, Elisabeth and Vogelezang, Suzanne and Wade, Kaitlin H and Wang, Carol A. and Wong, Andrew and Holm, Louise Aas and Chesi, Alessandra and Choong, Catherine and Cruz, Miguel and Elliott, Paul and Franks, Steve and Frithioff-Bøjsøe, Christine and Gauderman, W James and Glessner, Joseph T and Gilsanz, Vicente and Griesman, Kendra and Hanson, Robert L and Kaakinen, Marika and Kalkwarf, Heidi and Kelly, Andrea and Kindler, Joseph and Kähönen, Mika and Lanca, Carla and Lappe, Joan and Lee, Nanette R and McCormack, Shana and Mentch, Frank D and Mitchell, Jonathan A and Mononen, Nina and Niinikoski, Harri and Oken, Emily and Pahkala, Katja and Sim, Xueling and Teo, Yik-Ying and Baier, Leslie J and van Beijsterveldt, Toos and Adair, Linda S. and Boomsma, Dorret I. and de Geus, Eco and Guxens, Mònica and Eriksson, Johan G.
 and Felix, Janine F and Gilliland, Frank D and Biobank, Penn Medicine and Hansen, Torben and Hardy, Rebecca and Hivert, Marie-France and Holm, Jens-Christian and Jaddoe, Vincent W V and Järvelin, Marjo-Riitta and Lehtimäki, Terho and Mackey, David A and Meyre, David and Mohlke, Karen L and Mykkänen, Juha and Oberfield, Sharon and Pennell, Craig E and Perry, John R B and Raitakari, Olli and Rivadeneira, Fernando and Saw, Seang-Mei and Sebert, Sylvain and Shepherd, John A and Standl, Marie and Sørensen, Thorkild I A and Timpson, Nicholas J. and Torrent Quetglas, Maties and Willemsen, Gonneke and Hypponen, Elina and Power, Chris and McCarthy, Mark I and Freathy, Rachel M and Widen, Elisabeth and Hakonarson, Hakon and Prokopenko, Inga and Voight, Benjamin F and Zemel, Babette S and Grant, Struan F A and Cousminer, Diana L.
 },
}