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A saturated map of common genetic variants associated with human height


Yengo, L and Vedantam, S and Marouli, E and Sidorenko, J and Bartell, E and Sakaue, S and Graff, M and Eliasen, AU and Jiang, AU and Raghavan, S and Miao, J and Arias, JD and Graham, SE and Mukamel, RE and Spracklen, CN and Yin, X and Chen, SH and Ferreira, T and Highland, HH and Ji, Y and Karaderi, T and Lin, K and Lull, K and Medina-Gomez, C and Machado, M and Moore, A and Rueger, S and Sim, X and Vrieze, S and Ahluwalia, TS and Akiyama, M and Allison, MA and Alvarez, M and Andersen, MK and Ani, A and Appadurai, V and Arbeeva, L and Bhaskar, S and Bielak, LF and Bollepalli, S and Bonnycastle, LL and Bork-Jensen, J and Bradfield, JP and Bradford, Y and Braund, PS and Brody, JA and Burgdorf, KS and Cade, BE and Cai, H and Cai, Q and Campbell, A and Campbell, M and Catamo, E and Chai, JF and Chai, X and Chang, LC and Chang, YC and Chen, CH and Chesi, A and Choi, SH and Chung, RH and Cocca, M and Concas, MP and Couture, C and Cuellar-Partida, G and Danning, R and Daw, EW and Degenhard, F and Delgado, GE and Delitala, A and Demirkan, A and Deng, X and Devineni, P and Dietl, A and Dimitriou, M and Dimitrov, L and Dorajoo, R and Ekici, AB and Engmann, JE and Fairhurst-Hunter, Z and Faul, JD and Fernandez-Lopez, JC and Forer, L and Francescatto, M and Freitag-Wolf, S and Fuchsberger, C and Galesloot, TE and Gao, Y and Gao, Z and Geller, F and Giannakopoulou, O and Giulianini, F and Gjesing, AP and Goel, A and Goel, SD and Gorski, M and Grove, J and Hewitt, AW, 23andMe Research Team; VA Million Veteran Program; DiscovEHR (DiscovEHR and MyCode Community Health Initiative); eMERGE (Electronic Medical Records and Genomics Network); Lifelines Cohort Study; PRACTICAL Consortium; Understanding Society Scientific, A saturated map of common genetic variants associated with human height, Nature, 610, (7933) pp. 704-712. ISSN 0028-0836 (2022) [Refereed Article]

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DOI: doi:10.1038/s41586-022-05275-y


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 sizes1. 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 panel2) 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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetic immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:155581
Year Published:2022
Web of Science® Times Cited:13
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-03-01
Last Modified:2023-03-01

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