A common variant of HMGA2 is associated with adult and childhood height in the general population - PubMed (original) (raw)
. 2007 Oct;39(10):1245-50.
doi: 10.1038/ng2121. Epub 2007 Sep 2.
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; Diabetes Genetics Initiative; Wellcome Trust Case Control Consortium; George Davey Smith, Leif C Groop, Andrew T Hattersley, Mark I McCarthy, Joel N Hirschhorn, Timothy M Frayling
Affiliations
- PMID: 17767157
- PMCID: PMC3086278
- DOI: 10.1038/ng2121
A common variant of HMGA2 is associated with adult and childhood height in the general population
Michael N Weedon et al. Nat Genet. 2007 Oct.
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.
Figures
Figure 1
Quantile-quantile plot of 364,301 SNPs from the meta-analysis of DGI and WTCCC genome-wide association statistics. Blue dots represent observed statistics, and black line represents expected statistics.
Figure 2
Association, gene structure, conservation and linkage disequilibium of the HMGA2 gene region. (a) Plot of −log(P) versus chromosome position for the WTCCC and DGI meta-analysis. (b) Genomic location of genes showing intron and exon structure (NCBI build 35). (c) Multi-Z vertebrate alignment of 17 species showing evolutionary conservation. (d) Recombination rate given as cM/Mb. Red boxes represent recombination hotspots. (e) GOLDsurfer plot of linkage disequilibrium in HapMap CEU samples (expressed as pairwise _r_2).
Similar articles
- Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height.
Bouatia-Naji N, Marchand M, Cavalcanti-Proença C, Daghmoun S, Durand E, Tichet J, Marre M, Balkau B, Froguel P, Lévy-Marchal C. Bouatia-Naji N, et al. Eur J Endocrinol. 2009 Apr;160(4):557-60. doi: 10.1530/EJE-08-0794. Epub 2009 Jan 12. Eur J Endocrinol. 2009. PMID: 19139030 - HMGA2 is confirmed to be associated with human adult height.
Yang TL, Guo Y, Zhang LS, Tian Q, Yan H, Guo YF, Deng HW. Yang TL, et al. Ann Hum Genet. 2010 Jan;74(1):11-6. doi: 10.1111/j.1469-1809.2009.00555.x. Epub 2009 Nov 20. Ann Hum Genet. 2010. PMID: 19930247 Free PMC article. - Confirmation that SNPs in the high mobility group-A2 gene (HMGA2) are associated with adult height in the Japanese population; wide-ranging population survey of height-related SNPs in HMGA2.
Takeshita H, Fujihara J, Soejima M, Koda Y, Kimura-Kataoka K, Ono R, Yuasa I, Iida R, Ueki M, Nagao M, Yasuda T. Takeshita H, et al. Electrophoresis. 2011 Jul;32(14):1844-51. doi: 10.1002/elps.201100128. Electrophoresis. 2011. PMID: 21769890 - Genetic regulation of adult stature.
Lettre G. Lettre G. Curr Opin Pediatr. 2009 Aug;21(4):515-22. doi: 10.1097/MOP.0b013e32832c6dce. Curr Opin Pediatr. 2009. PMID: 19455035 Review. - Recent progress in the study of the genetics of height.
Lettre G. Lettre G. Hum Genet. 2011 May;129(5):465-72. doi: 10.1007/s00439-011-0969-x. Epub 2011 Feb 22. Hum Genet. 2011. PMID: 21340692 Review.
Cited by
- Height matters-from monogenic disorders to normal variation.
Durand C, Rappold GA. Durand C, et al. Nat Rev Endocrinol. 2013 Mar;9(3):171-7. doi: 10.1038/nrendo.2012.251. Epub 2013 Jan 22. Nat Rev Endocrinol. 2013. PMID: 23337954 Review. - HMGA2 and high-grade serous ovarian carcinoma.
Wu J, Wei JJ. Wu J, et al. J Mol Med (Berl). 2013 Oct;91(10):1155-65. doi: 10.1007/s00109-013-1055-8. Epub 2013 May 19. J Mol Med (Berl). 2013. PMID: 23686260 Review. - The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells.
Copley MR, Babovic S, Benz C, Knapp DJ, Beer PA, Kent DG, Wohrer S, Treloar DQ, Day C, Rowe K, Mader H, Kuchenbauer F, Humphries RK, Eaves CJ. Copley MR, et al. Nat Cell Biol. 2013 Aug;15(8):916-25. doi: 10.1038/ncb2783. Epub 2013 Jun 30. Nat Cell Biol. 2013. PMID: 23811688 - Genetic research into bipolar disorder: the need for a research framework that integrates sophisticated molecular biology and clinically informed phenotype characterization.
Schulze TG. Schulze TG. Psychiatr Clin North Am. 2010 Mar;33(1):67-82. doi: 10.1016/j.psc.2009.10.005. Psychiatr Clin North Am. 2010. PMID: 20159340 Free PMC article. Review. - Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.
Lopera-Maya EA, Kurilshikov A, van der Graaf A, Hu S, Andreu-Sánchez S, Chen L, Vila AV, Gacesa R, Sinha T, Collij V, Klaassen MAY, Bolte LA, Gois MFB, Neerincx PBT, Swertz MA; LifeLines Cohort Study; Harmsen HJM, Wijmenga C, Fu J, Weersma RK, Zhernakova A, Sanna S. Lopera-Maya EA, et al. Nat Genet. 2022 Feb;54(2):143-151. doi: 10.1038/s41588-021-00992-y. Epub 2022 Feb 3. Nat Genet. 2022. PMID: 35115690
References
- Fisher RA. The correlation between relatives on the supposition of mendelian inheritance. Trans. R. Soc. Edinburgh. 1918:399–433.
- Macgregor S, Cornes BK, Martin NG, Visscher PM. Bias, precision and heritability of self-reported and clinically measured height in Australian twins. Hum. Genet. 2006;120:571–580. - PubMed
- Preece MA. The genetic contribution to stature. Horm. Res. 1996;45:56–58. - PubMed
- Silventoinen K, et al. Heritability of adult body height: A comparative study of twin cohorts in eight countries. Twin Res. 2003;6:399–408. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- 079557/WT_/Wellcome Trust/United Kingdom
- G0500070/MRC_/Medical Research Council/United Kingdom
- U01 HG004171/HG/NHGRI NIH HHS/United States
- G9815508(74882)/MRC_/Medical Research Council/United Kingdom
- 076467/WT_/Wellcome Trust/United Kingdom
- 072960/WT_/Wellcome Trust/United Kingdom
- 076113/WT_/Wellcome Trust/United Kingdom
- G0600705/MRC_/Medical Research Council/United Kingdom
- 090532/WT_/Wellcome Trust/United Kingdom
- G9815508/MRC_/Medical Research Council/United Kingdom
- WT_/Wellcome Trust/United Kingdom
- GR072960/WT_/Wellcome Trust/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials