A Saturated Map of Common Genetic Variants Associated with Human Height

Citation

Yengo, Loïc; Vedantam, Sailaja; Marouli, Eirini; Sidorenko, Julia; Bartell, Eric; Sakaue, Saori; Graff, Mariaelisa; Eliasen, Anders U.; Jiang, Yunxuan; & Raghavan, Sridharan, et al. (2022). A Saturated Map of Common Genetic Variants Associated with Human Height. Nature, 610, 704-712. PMCID: PMC9605867

Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

URL

http://dx.doi.org/10.1038/s41586-022-05275-y

Reference Type

Journal Article

Year Published

2022

Journal Title

Nature

Author(s)

Yengo, Loïc
Vedantam, Sailaja
Marouli, Eirini
Sidorenko, Julia
Bartell, Eric
Sakaue, Saori
Graff, Mariaelisa
Eliasen, Anders U.
Jiang, Yunxuan
Raghavan, Sridharan
Miao, Jenkai
Arias, Joshua D.
Graham, Sarah E.
Mukamel, Ronen E.
Spracklen, Cassandra N.
Yin, Xianyong
Chen, Shyh-Huei
Ferreira, Teresa
Highland, Heather H.
Ji, Yingjie
Karaderi, Tugce
Lin, Kuang
Lüll, Kreete
Malden, Deborah E.
Medina-Gomez, Carolina
Machado, Moara
Moore, Amy
Rüeger, Sina
Sim, Xueling
Vrieze, Scott
Ahluwalia, Tarunveer S.
Akiyama, Masato
Allison, Matthew A.
Alvarez, Marcus
Andersen, Mette K.
Ani, Alireza
Appadurai, Vivek
Arbeeva, Liubov
Bhaskar, Seema
Bielak, Lawrence F.
Bollepalli, Sailalitha
Bonnycastle, Lori L.
Bork-Jensen, Jette
Bradfield, Jonathan P.
Bradford, Yuki
Braund, Peter S.
Brody, Jennifer A.
Burgdorf, Kristoffer S.
Cade, Brian E.
Cai, Hui
Cai, Qiuyin
Campbell, Archie
Cañadas-Garre, Marisa
Catamo, Eulalia
Chai, Jin Fang
Chai, Xiaoran
Chang, Li-Ching
Chang, Yi-Cheng
Chen, Chien-Hsiun
Chesi, Alessandra
Choi, Seung Hoan
Chung, Ren-Hua
Cocca, Massimiliano
Concas, Maria Pina
Couture, Christian
Cuellar-Partida, Gabriel
Danning, Rebecca
Daw, E. Warwick
Degenhard, Frauke
Delgado, Graciela E.
Delitala, Alessandro
Demirkan, Ayse
Deng, Xuan
Devineni, Poornima
Dietl, Alexander
Dimitriou, Maria
Dimitrov, Latchezar
Dorajoo, Rajkumar
Ekici, Arif B.
Engmann, Jorgen E.
Fairhurst-Hunter, Zammy
Farmaki, Aliki-Eleni
Faul, Jessica D.
Fernandez-Lopez, Juan Carlos
Forer, Lukas
Francescatto, Margherita
Freitag-Wolf, Sandra
Fuchsberger, Christian
Galesloot, Tessel E.
Gao, Yan
Gao, Zishan
Geller, Frank
Giannakopoulou, Olga
Giulianini, Franco
Gjesing, Anette P.
Goel, Anuj
Gordon, Scott D.
Gorski, Mathias
Grove, Jakob
Guo, Xiuqing
Gustafsson, Stefan
Haessler, Jeffrey
Hansen, Thomas F.
Havulinna, Aki S.
Haworth, Simon J.
He, Jing
Heard-Costa, Nancy L.
Hebbar, Prashantha
Hindy, George
Ho, Yuk-Lam A.
Hofer, Edith
Holliday, Elizabeth G.
Horn, Katrin
Hornsby, Whitney E.
Hottenga, Jouke-Jan
Huang, Hongyan
Huang, Jie
Huerta-Chagoya, Alicia
Huffman, Jennifer E.
Hung, Yi-Jen
Huo, Shaofeng
Hwang, Mi Yeong
Iha, Hiroyuki
Ikeda, Daisuke D.
Isono, Masato
Jackson, Anne U.
Jäger, Susanne
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Wilkens, Lynne R.
Willemsen, Gonneke
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Wright, Alan F.
Wu, Jer-Yuarn
Xu, Huichun
Yajnik, Chittaranjan S.
Yokota, Mitsuhiro
Yuan, Jian-Min
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Zemel, Babette S.
Zheng, Wei
Zhu, Xiaofeng
Zmuda, Joseph M.
Zonderman, Alan B.
Zwart, John-Anker
Chasman, Daniel I.
Cho, Yoon Shin
Heid, Iris M.
McCarthy, Mark I.
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Rivadeneira, Fernando
Thorsteinsdottir, Unnur
Sun, Yan V.
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Loos, Ruth J. F.
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Yang, Jian
Esko, Tõnu
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Hirschhorn, Joel N.

Article Type

Regular

PMCID

PMC9605867

Continent/Country

Nonspecific

Race/Ethnicity

European Ancestry
Hispanic Ancestry
African Ancestry
South Asian Ancestry

ORCiD

Adair - 0000-0002-3670-8073