Letter abstract
Nature Genetics 39, 1245 - 1250 (2007)
Published online: 2 September 2007 | doi:10.1038/ng2121
A common variant of HMGA2 is associated with adult and childhood height in the general population
Michael N Weedon1,2,21, Guillaume Lettre3,4,21, Rachel M Freathy1,2,21, Cecilia M Lindgren5,6,21, Benjamin F Voight3,7, John R B Perry1,2, Katherine S Elliott5, Rachel Hackett3, Candace Guiducci3, Beverley Shields2, Eleftheria Zeggini5, Hana Lango1,2, Valeriya Lyssenko8,9, Nicholas J Timpson5,10, Noel P Burtt3, Nigel W Rayner6, Richa Saxena3,7,11, Kristin Ardlie3, Jonathan H Tobias12, Andrew R Ness13, Susan M Ring14, Colin N A Palmer15, Andrew D Morris16, Leena Peltonen3,17,18, Veikko Salomaa19, The Diabetes Genetics Initiative, The Wellcome Trust Case Control Consortium, George Davey Smith10, Leif C Groop8,9, Andrew T Hattersley1,2, Mark I McCarthy5,6,21, Joel N Hirschhorn3,4,20,21 & Timothy M Frayling1,2,21
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.
- Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.
- Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
- Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA.
- Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
- Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, 205 02 Malmö, Sweden.
- Department of Medicine, Helsinki University Central Hospital, Folkhalsan Genetic Institute, Folkhalsan Research Center and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland.
- The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK.
- Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
- Clinical Science at South Bristol, University of Bristol, Bristol BS2 8AE, UK.
- Department of Oral and Dental Science, Bristol Dental School, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK.
- Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK.
- Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
- Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
- Department of Molecular Medicine, National Public Health Institute, Biomedicum, FI-00290 Helsinki, Finland.
- Department of Medical Genetics, University of Helsinki, FI-00014 Helsinki, Finland.
- Department of Epidemiology and Health Promotion, National Public Health Institute, FI-00300 Helsinki, Finland.
- Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
- These authors contributed equally to this work.
Correspondence to: Timothy M Frayling1,2,21 e-mail: Tim.Frayling@pms.ac.uk
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