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Identification of ten loci associated with height highlights new biological pathways in human growth

Lettre, Guillaume; Jackson, Anne U.; Gieger, Christian; Schumacher, Fredrick R.; Berndt, Sonja I.; Sanna, Serena; Eyheramendy, Susana; Voight, Benjamin F.; Butler, Johannah L. and Guiducci, Candace, et al. (2008) In Nature Genetics 40(5). p.584-591
Abstract
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet- undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in 410,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for similar to 2% of the population variation in height. Individuals with <= 8 height-increasing alleles and >= 16 height-increasing alleles differ in height by similar to 3.5 cm. The newly identified loci, along with several additional loci with strongly... (More)
Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet- undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in 410,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for similar to 2% of the population variation in height. Individuals with <= 8 height-increasing alleles and >= 16 height-increasing alleles differ in height by similar to 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. (Less)
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Nature Genetics
volume
40
issue
5
pages
584 - 591
publisher
Nature Publishing Group
external identifiers
  • wos:000255366700026
  • scopus:42649092874
ISSN
1546-1718
DOI
10.1038/ng.125
language
English
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yes
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ce9240ff-d437-4665-8a68-9402c329cdfd (old id 1205108)
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2008-09-18 13:45:40
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2017-08-13 03:58:55
@article{ce9240ff-d437-4665-8a68-9402c329cdfd,
  abstract     = {Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet- undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in 410,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for similar to 2% of the population variation in height. Individuals with &lt;= 8 height-increasing alleles and &gt;= 16 height-increasing alleles differ in height by similar to 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.},
  author       = {Lettre, Guillaume and Jackson, Anne U. and Gieger, Christian and Schumacher, Fredrick R. and Berndt, Sonja I. and Sanna, Serena and Eyheramendy, Susana and Voight, Benjamin F. and Butler, Johannah L. and Guiducci, Candace and Illig, Thomas and Hackett, Rachel and Heid, Iris M. and Jacobs, Kevin B. and Lyssenko, Valeriya and Uda, Manuela and Boehnke, Michael and Chanock, Stephen J. and Groop, Leif and Hu, Frank B. and Isomaa, Bo and Kraft, Peter and Peltonen, Leena and Salomaa, Veikko and Schlessinger, David and Hunter, David J. and Hayes, Richard B. and Abecasis, Goncalo R. and Wichmann, H-Erich and Mohlke, Karen L. and Hirschhorn, Joel N.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {5},
  pages        = {584--591},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Identification of ten loci associated with height highlights new biological pathways in human growth},
  url          = {http://dx.doi.org/10.1038/ng.125},
  volume       = {40},
  year         = {2008},
}