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

MN Weedon; G Lettre; RM Freathy; CM Lindgren; BF Voight; JR Perry; KS Elliott; R Hackett; C Guiducci; B Shields; E Zeggini; H Lango; V Lyssenko; N J Timpson; NP Burtt; NW Rayner; R Saxena; K Ardlie; Jonathan H Tobias; A Ness; SM Ring; CN Palmer; AD Morris; L Peltonen; V Salomaa; Initiative The Diabetes Genetics; Consortium The Wellcome Trust Case Control; George Davey Smith; LC Groop; AT Hattersley; MI McCarthy; JN Hirschhorn; TM Frayling

doi:10.1038/ng2121

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

MN Weedon, G Lettre, RM Freathy, CM Lindgren, BF Voight, JR Perry, KS Elliott, R Hackett, C Guiducci, B Shields, E Zeggini, H Lango, V Lyssenko, N J Timpson, NP Burtt, NW Rayner, R Saxena, K Ardlie, Jonathan H Tobias, A NessSM Ring, CN Palmer, AD Morris, L Peltonen, V Salomaa, Initiative The Diabetes Genetics, Consortium The Wellcome Trust Case Control, George Davey Smith, LC Groop, AT Hattersley, MI McCarthy, JN Hirschhorn, TM Frayling

Research output: Contribution to journal › Article (Academic Journal) › peer-review

311 Citations (Scopus)

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 x 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 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 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.

Translated title of the contribution	A common variant of HMGA2 is associated with adult and childhood height in the general population
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 - Oct 2007

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Publisher: Nature Publishing Group

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Weedon, MN., Lettre, G., Freathy, RM., Lindgren, CM., Voight, BF., Perry, JR., Elliott, KS., Hackett, R., Guiducci, C., Shields, B., Zeggini, E., Lango, H., Lyssenko, V., Timpson, N. J., Burtt, NP., Rayner, NW., Saxena, R., Ardlie, K., Tobias, J. H., ... Frayling, TM. (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

Weedon, MN ; Lettre, G ; Freathy, RM ; Lindgren, CM ; Voight, BF ; Perry, JR ; Elliott, KS ; Hackett, R ; Guiducci, C ; Shields, B ; Zeggini, E ; Lango, H ; Lyssenko, V ; Timpson, N J ; Burtt, NP ; Rayner, NW ; Saxena, R ; Ardlie, K ; Tobias, Jonathan H ; Ness, A ; Ring, SM ; Palmer, CN ; Morris, AD ; Peltonen, L ; Salomaa, V ; The Diabetes Genetics, Initiative ; The Wellcome Trust Case Control, Consortium ; Davey Smith, George ; Groop, LC ; Hattersley, AT ; McCarthy, MI ; Hirschhorn, JN ; Frayling, TM. / A common variant of HMGA2 is associated with adult and childhood height in the general population. In: Nature Genetics. 2007 ; Vol. 39, No. 10. pp. 1245 - 1250.

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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 x 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 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 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 = "MN Weedon and G Lettre and RM Freathy and CM Lindgren and BF Voight and JR Perry and KS Elliott and R Hackett and C Guiducci and B Shields and E Zeggini and H Lango and V Lyssenko and Timpson, {N J} and NP Burtt and NW Rayner and R Saxena and K Ardlie and Tobias, {Jonathan H} and A Ness and SM Ring and CN Palmer and AD Morris and L Peltonen and V Salomaa and {The Diabetes Genetics}, Initiative and {The Wellcome Trust Case Control}, Consortium and {Davey Smith}, George and LC Groop and AT Hattersley and MI McCarthy and JN Hirschhorn and TM Frayling",

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year = "2007",

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doi = "10.1038/ng2121",

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Weedon, MN, Lettre, G, Freathy, RM, Lindgren, CM, Voight, BF, Perry, JR, 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, A , Ring, SM, Palmer, CN, Morris, AD, Peltonen, L, Salomaa, V, The Diabetes Genetics, I, The Wellcome Trust Case Control, C, Davey Smith, G, 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

A common variant of HMGA2 is associated with adult and childhood height in the general population. / Weedon, MN; Lettre, G; Freathy, RM; Lindgren, CM; Voight, BF; Perry, JR; Elliott, KS; Hackett, R; Guiducci, C; Shields, B; Zeggini, E; Lango, H; Lyssenko, V; Timpson, N J; Burtt, NP; Rayner, NW; Saxena, R; Ardlie, K; Tobias, Jonathan H ; Ness, A ; Ring, SM; Palmer, CN; Morris, AD; Peltonen, L; Salomaa, V; The Diabetes Genetics, Initiative; The Wellcome Trust Case Control, Consortium; Davey Smith, George; Groop, LC; Hattersley, AT; McCarthy, MI; Hirschhorn, JN; Frayling, TM.

In: Nature Genetics, Vol. 39, No. 10, 10.2007, p. 1245 - 1250.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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AU - Weedon, MN

AU - Lettre, G

AU - Freathy, RM

AU - Lindgren, CM

AU - Voight, BF

AU - Perry, JR

AU - Elliott, KS

AU - Hackett, R

AU - Guiducci, C

AU - Shields, B

AU - Zeggini, E

AU - Lango, H

AU - Lyssenko, V

AU - Timpson, N J

AU - Burtt, NP

AU - Rayner, NW

AU - Saxena, R

AU - Ardlie, K

AU - Tobias, Jonathan H

AU - Ness, A

AU - Ring, SM

AU - Palmer, CN

AU - Morris, AD

AU - Peltonen, L

AU - Salomaa, V

AU - The Diabetes Genetics, Initiative

AU - The Wellcome Trust Case Control, Consortium

AU - Davey Smith, George

AU - Groop, LC

AU - Hattersley, AT

AU - McCarthy, MI

AU - Hirschhorn, JN

AU - Frayling, TM

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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 x 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 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 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 x 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 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 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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DO - 10.1038/ng2121

M3 - Article (Academic Journal)

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EP - 1250

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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ER -

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

Abstract

Bibliographical note

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CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)

Cite this