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

Michael N. Weedon, Guillaume Lettre, Rachel M. Freathy, Cecilia M. Lindgren, Benjamin F. Voight, John R.B. Perry, Katherine S. Elliott, Rachel Hackett, Candace Guiducci, Beverley Shields, Eleftheria Zeggini, Hana Lango, Valeriya Lyssenko, Nicholas J. Timpson, Noel P. Burtt, Nigel W. Rayner, Richa Saxena, Kristin Ardlie, Jonathan H. Tobias, Andrew R. NessSusan M. Ring, Colin N.A. Palmer, Andrew D. Morris, Leena Peltonen, Veikko Salomaa, George Davey Smith, Leif C. Groop, Andrew T. Hattersley, Mark I. McCarthy, Joel N. Hirschhorn, Timothy M. Frayling

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    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 = 4 × 10 -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 = 3 × 10-11, overall P = 4 × 10-16, including the genome-wide association data). We also observed the association in children (P = 1 × 10-6, N = 6,827) and a tall/short case-control study (P = 4 × 10-6, N = 3,207). We estimate that rs1042725 explains ∼0.3% of population variation in height (∼0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.

    Original languageEnglish
    Pages (from-to)1245-1250
    Number of pages6
    JournalNature Genetics
    Volume39
    Issue number10
    DOIs
    Publication statusPublished - 1 Oct 2007

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    Weedon, M. N., Lettre, G., Freathy, R. M., Lindgren, C. M., Voight, B. F., Perry, J. R. B., Elliott, K. S., Hackett, R., Guiducci, C., Shields, B., Zeggini, E., Lango, H., Lyssenko, V., Timpson, N. J., Burtt, N. P., Rayner, N. W., Saxena, R., Ardlie, K., Tobias, J. H., ... Frayling, T. M. (2007). A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genetics, 39(10), 1245-1250. https://doi.org/10.1038/ng2121