The results of the research may help doctors identify patients who are unable to grow to their genetically projected height, which may subsequently facilitate the identification of undiagnosed diseases or conditions that may be preventing them from growing normally or negatively affecting their health.
The research was the largest-ever genome-wide association study.
The study, which was recently published in the journal Nature, is the largest genome-wide association study ever conducted, using the DNA of nearly 5 million individuals from 281 contributing studies. It fills a significant gap in our knowledge of how genetic differences contribute to height differences. Over one million research participants are of non-European heritage (African, East Asian, Hispanic, or South Asian).
The 12,111 variants that cluster around areas of the genome involved with skeletal growth offer a strong genetic predictor of height. For people of European ancestry, the identified variants account for 40% of the variance in height, and for those of non-European ancestry, 10–20%.
Adult height is mostly determined by the information encoded in our DNA; children of tall parents are likely to be taller, while children of short parents tend to be shorter, although these estimations aren’t perfect. The development of a small baby into an adult, as well as the role of genetics in this process, has long been a complicated and poorly understood aspect of human biology. The previous largest genome-wide association study on height employed a sample size of up to 700,000 people; the current sample is around seven times larger than earlier studies.
The study, which is being conducted at a scale never before seen, offers new levels of biological detail and understanding of why individuals are tall or short, with heredity being connected to various specific genomic regions. The results demonstrate that regions comprising just over 20% of the genome contain the majority of the gene variants linked to height.
The study’s findings could help doctors identify people who cannot reach their genetically predicted height, which may aid in the diagnosis of hidden diseases or conditions that may be stunting their growth or impacting their health. The research also provides a valuable blueprint on how it could be possible to use genome-wide studies to identify a disease’s biology and subsequently its hereditary components.
Greater genomic diversity needed
While this study has a large number of participants from non-European ancestries compared to previous studies, the researchers emphasize the need for more diversity in genomic research.
Most of the genetic data available are from people of European ancestry, so genome-wide studies don’t capture the wide range of ancestral diversity across the globe. Increasing the size of genome-wide studies in non-European ancestry populations is essential to achieve the same saturation level and close the gap in prediction accuracy in different populations.
Dr. Eirini Marouli, a co-first author of the study and Senior Lecturer in Computational Biology at Queen Mary University of London, said: “We have accomplished a feat in studying the DNA of over 5 million people that was broadly considered impossible until recently.”
She continues, “Genomic studies are revolutionary and might hold the key to solving many global health challenges – their potential is tremendously exciting. If we can get a clear picture of a trait such as height at a genomic level, we may then have the model to better diagnose and treat gene-influenced conditions like heart disease or schizophrenia, for example. If we can map specific parts of the genome to certain traits, it opens the door to widespread targeted, personalized treatments further down the line that could benefit people everywhere.”
Reference: “A saturated map of common genetic variants associated with human height” by Loïc Yengo, Sailaja Vedantam, Eirini Marouli, Julia Sidorenko, Eric Bartell, Saori Sakaue, Marielisa Graff, Anders U. Eliasen, Yunxuan Jiang, Sridharan Raghavan, Jenkai Miao, Joshua D. Arias, Sarah E. Graham, Ronen E. Mukamel, Cassandra N. Spracklen, Xianyong Yin, Shyh-Huei Chen, Teresa Ferreira, Heather H. Highland, Yingjie Ji, Tugce Karaderi, Kuang Lin, Kreete Lüll, Deborah E. Malden, Carolina Medina-Gomez, Moara Machado, Amy Moore, Sina Rüeger, Xueling Sim, Scott Vrieze, Tarunveer S. Ahluwalia, Masato Akiyama, Matthew A. Allison, Marcus Alvarez, Mette K. Andersen, Alireza Ani, Vivek Appadurai, Liubov Arbeeva, Seema Bhaskar, Lawrence F. Bielak, Sailalitha Bollepalli, Lori L. Bonnycastle, Jette Bork-Jensen, Jonathan P. Bradfield, Yuki Bradford, Peter S. Braund, Jennifer A. Brody, Kristoffer S. Burgdorf, Brian E. Cade, Hui Cai, Qiuyin Cai, Archie Campbell, Marisa Cañadas-Garre, Eulalia Catamo, Jin-Fang Chai, Xiaoran Chai, Li-Ching Chang, Yi-Cheng Chang, Chien-Hsiun Chen, Alessandra Chesi, Seung Hoan Choi, Ren-Hua Chung, Massimiliano Cocca, Maria Pina Concas, Christian Couture, Gabriel Cuellar-Partida, Rebecca Danning, E. Warwick Daw, Frauke Degenhard, Graciela E. Delgado, Alessandro Delitala, Ayse Demirkan, Xuan Deng, Poornima Devineni, Alexander Dietl, Maria Dimitriou, Latchezar Dimitrov, Rajkumar Dorajoo, Arif B. Ekici, Jorgen E. Engmann, Zammy Fairhurst-Hunter, Aliki-Eleni Farmaki, Jessica D. Faul, Juan-Carlos Fernandez-Lopez, Lukas Forer, Margherita Francescatto, Sandra Freitag-Wolf, Christian Fuchsberger, Tessel E. Galesloot, Yan Gao, Zishan Gao, Frank Geller, Olga Giannakopoulou, Franco Giulianini, Anette P. Gjesing, Anuj Goel, Scott D. Gordon, Mathias Gorski, Jakob Grove, Xiuqing Guo, Stefan Gustafsson, Jeffrey Haessler, Thomas F. Hansen, Aki S. Havulinna, Simon J. Haworth, Jing He, Nancy Heard-Costa, Prashantha Hebbar, George Hindy, Yuk-Lam A. Ho, Edith Hofer, Elizabeth Holliday, Katrin Horn, Whitney E. Hornsby, Jouke-Jan Hottenga, Hongyan Huang, Jie Huang, Alicia Huerta-Chagoya, Jennifer E. Huffman, Yi-Jen Hung, Shaofeng Huo, Mi Yeong Hwang, Hiroyuki Iha, Daisuke D. Ikeda, Masato Isono, Anne U. Jackson, Susanne Jäger, Iris E. Jansen, Ingegerd Johansson, Jost B. Jonas, Anna Jonsson, Torben Jørgensen, Ioanna-Panagiota Kalafati, Masahiro Kanai, Stavroula Kanoni, Line L. Kårhus, Anuradhani Kasturiratne, Tomohiro Katsuya, Takahisa Kawaguchi, Rachel L. Kember, Katherine A. Kentistou, Han-Na Kim, Young Jin Kim, Marcus E. Kleber, Maria J. Knol, Azra Kurbasic, … Michael Boehnke, Panos Deloukas, Anne E. Justice, Cecilia M. Lindgren, Ruth J. F. Loos, Karen L. Mohlke, Kari E. North, Kari Stefansson, Robin G. Walters, Thomas W. Winkler, Kristin L. Young, Po-Ru Loh, Jian Yang, Tõnu Esko, Themistocles L. Assimes, Adam Auton, Goncalo R. Abecasis, Cristen J. Willer, Adam E. Locke, Sonja I. Berndt, Guillaume Lettre, Timothy M. Frayling, Yukinori Okada, Andrew R. Wood, Peter M. Visscher, and Joel N. Hirschhorn, 12 October 2022, Nature.
DOI: 10.1038/s41586-022-05275-y
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