Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
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 Aas; 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; Guxens, Mònica; Eriksson, Johan G; Felix, Janine F; Gilliland, Frank D; Biobank, Penn Medicine; 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; 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; ,; 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 (2024-01-16)
Biomed central
16.01.2024
Bradfield, J.P., Kember, R.L., Ulrich, A. et al. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes. Genome Biol 25, 22 (2024). https://doi.org/10.1186/s13059-023-03136-z
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https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202401311507
https://urn.fi/URN:NBN:fi:oulu-202401311507
Tiivistelmä
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.
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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