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A common variant of HMGA2 is associated with adult and childhood height in the general population

Weedon, Michael N.; Lettre, Guillaume; Freathy, Rachel M.; Lindgren, Cecilia M.; Voight, Benjamin F.; Perry, John R. B.; Elliott, Katherine S.; Hackett, Rachel; Guiducci, Candace and Shields, Beverley, et al. (2007) In Nature Genetics 39(10). p.1245-1250
Abstract
Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6),... (More)
Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6), N=3,207). We estimate that rs1042725 explains similar to 0.3% of population variation in height (similar to 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitative traits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height. (Less)
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@article{4af0d455-41fa-47be-ba6f-6397106760a5,
  abstract     = {Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6), N=3,207). We estimate that rs1042725 explains similar to 0.3% of population variation in height (similar to 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitative traits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.},
  author       = {Weedon, Michael N. and Lettre, Guillaume and Freathy, Rachel M. and Lindgren, Cecilia M. and Voight, Benjamin F. and Perry, John R. B. and Elliott, Katherine S. and Hackett, Rachel and Guiducci, Candace and Shields, Beverley and Zeggini, Eleftheria and Lango, Hana and Lyssenko, Valeriya and Timpson, Nicholas J. and Burtt, Noel P. and Rayner, Nigel W. and Saxena, Richa and Ardlie, Kristin and Tobias, Jonathan H. and Ness, Andrew R. and Ring, Susan M. and Palmer, Colin N. A. and Morris, Andrew D. and Peltonen, Leena and Salomaa, Veikko and Smith, George Davey and Groop, Leif and Hattersley, Andrew T. and McCarthy, Mark I. and Hirschhorn, Joel N. and Frayling, Timothy M.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {10},
  pages        = {1245--1250},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {A common variant of HMGA2 is associated with adult and childhood height in the general population},
  url          = {http://dx.doi.org/10.1038/ng2121},
  volume       = {39},
  year         = {2007},
}