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A saturated map of common genetic variants associated with human height.

Publication ,  Journal Article
Yengo, L; Vedantam, S; Marouli, E; Sidorenko, J; Bartell, E; Sakaue, S; Graff, M; Eliasen, AU; Jiang, Y; Raghavan, S; Miao, J; Arias, JD ...
Published in: Nature
October 2022

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 2022

Volume

610

Issue

7933

Start / End Page

704 / 712

Location

England

Related Subject Headings

  • Sample Size
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genome-Wide Association Study
  • Genome, Human
  • General Science & Technology
  • Gene Frequency
 

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Yengo, L., Vedantam, S., Marouli, E., Sidorenko, J., Bartell, E., Sakaue, S., … Rhee, S. Y. (2022). A saturated map of common genetic variants associated with human height. Nature, 610(7933), 704–712. https://doi.org/10.1038/s41586-022-05275-y
Yengo, Loïc, Sailaja Vedantam, Eirini Marouli, Julia Sidorenko, Eric Bartell, Saori Sakaue, Marielisa Graff, et al. “A saturated map of common genetic variants associated with human height.Nature 610, no. 7933 (October 2022): 704–12. https://doi.org/10.1038/s41586-022-05275-y.
Yengo L, Vedantam S, Marouli E, Sidorenko J, Bartell E, Sakaue S, et al. A saturated map of common genetic variants associated with human height. Nature. 2022 Oct;610(7933):704–12.
Yengo, Loïc, et al. “A saturated map of common genetic variants associated with human height.Nature, vol. 610, no. 7933, Oct. 2022, pp. 704–12. Pubmed, doi:10.1038/s41586-022-05275-y.
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LT, Morgan A, Mucha S, Munz M, Nakatochi M, Nelson CP, Nethander M, Nho CW, Nielsen AA, Nolte IM, Nongmaithem SS, Noordam R, Ntalla I, Nutile T, Pandit A, Christofidou P, Pärna K, Pauper M, Petersen ERB, Petersen LV, Pitkänen N, Polašek O, Poveda A, Preuss MH, Pyarajan S, Raffield LM, Rakugi H, Ramirez J, Rasheed A, Raven D, Rayner NW, Riveros C, Rohde R, Ruggiero D, Ruotsalainen SE, Ryan KA, Sabater-Lleal M, Saxena R, Scholz M, Sendamarai A, Shen B, Shi J, Shin JH, Sidore C, Sitlani CM, Slieker RC, Smit RAJ, Smith AV, Smith JA, Smyth LJ, Southam L, Steinthorsdottir V, Sun L, Takeuchi F, Tallapragada DSP, Taylor KD, Tayo BO, Tcheandjieu C, Terzikhan N, Tesolin P, Teumer A, Theusch E, Thompson DJ, Thorleifsson G, Timmers PRHJ, Trompet S, Turman C, Vaccargiu S, van der Laan SW, van der Most PJ, van Klinken JB, van Setten J, Verma SS, Verweij N, Veturi Y, Wang CA, Wang C, Wang L, Wang Z, Warren HR, Bin Wei W, Wickremasinghe AR, Wielscher M, Wiggins KL, Winsvold BS, Wong A, Wu Y, Wuttke M, 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Vidal PM, Martin NG, März W, Matsuda F, McGarrah RW, McGue M, McKnight AJ, Medland SE, Mellström D, Metspalu A, Mitchell BD, Mitchell P, Mook-Kanamori DO, Morris AD, Mucci LA, Munroe PB, Nalls MA, Nazarian S, Nelson AE, Neville MJ, Newton-Cheh C, Nielsen CS, Nöthen MM, Ohlsson C, Oldehinkel AJ, Orozco L, Pahkala K, Pajukanta P, Palmer CNA, Parra EJ, Pattaro C, Pedersen O, Pennell CE, Penninx BWJH, Perusse L, Peters A, Peyser PA, Porteous DJ, Posthuma D, Power C, Pramstaller PP, Province MA, Qi Q, Qu J, Rader DJ, Raitakari OT, Ralhan S, Rallidis LS, Rao DC, Redline S, Reilly DF, Reiner AP, Rhee SY. A saturated map of common genetic variants associated with human height. Nature. 2022 Oct;610(7933):704–712.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 2022

Volume

610

Issue

7933

Start / End Page

704 / 712

Location

England

Related Subject Headings

  • Sample Size
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genome-Wide Association Study
  • Genome, Human
  • General Science & Technology
  • Gene Frequency