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. Ness; Susan 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

doi:10.1038/ng2121

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 language	English
Pages (from-to)	1245-1250
Number of pages	6
Journal	Nature Genetics
Volume	39
Issue number	10
DOIs	https://doi.org/10.1038/ng2121
Publication status	Published - 1 Oct 2007

ASJC Scopus subject areas

Genetics

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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

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

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.",

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

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Weedon, MN, Lettre, G, Freathy, RM, Lindgren, CM, Voight, BF, Perry, JRB, Elliott, KS, Hackett, R, Guiducci, C, Shields, B, Zeggini, E, Lango, H, Lyssenko, V, Timpson, NJ, Burtt, NP, Rayner, NW, Saxena, R, Ardlie, K, Tobias, JH, Ness, AR, Ring, SM, Palmer, CNA, Morris, AD, Peltonen, L, Salomaa, V, Smith, GD, Groop, LC, Hattersley, AT, McCarthy, MI, Hirschhorn, JN & Frayling, TM 2007, 'A common variant of HMGA2 is associated with adult and childhood height in the general population', Nature Genetics, vol. 39, no. 10, pp. 1245-1250. https://doi.org/10.1038/ng2121

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AU - Weedon, Michael N.

AU - Lettre, Guillaume

AU - Freathy, Rachel M.

AU - Lindgren, Cecilia M.

AU - Voight, Benjamin F.

AU - Perry, John R.B.

AU - Elliott, Katherine S.

AU - Hackett, Rachel

AU - Guiducci, Candace

AU - Shields, Beverley

AU - Zeggini, Eleftheria

AU - Lango, Hana

AU - Lyssenko, Valeriya

AU - Timpson, Nicholas J.

AU - Burtt, Noel P.

AU - Rayner, Nigel W.

AU - Saxena, Richa

AU - Ardlie, Kristin

AU - Tobias, Jonathan H.

AU - Ness, Andrew R.

AU - Ring, Susan M.

AU - Palmer, Colin N.A.

AU - Morris, Andrew D.

AU - Peltonen, Leena

AU - Salomaa, Veikko

AU - Smith, George Davey

AU - Groop, Leif C.

AU - Hattersley, Andrew T.

AU - McCarthy, Mark I.

AU - Hirschhorn, Joel N.

AU - Frayling, Timothy M.

PY - 2007/10/1

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N2 - 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.

AB - 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.

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

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