High and mighty: first common height gene identified by researchers behind 'obesity gene' finding

Sunday 2 September 2007, 18.00

While we all know that tall parents are more likely to have tall children, scientists have been unable to identify any common genes that make people taller than others. Now, however, scientists have identified the first gene, known as HMGA2, a common variant of which directly influences height.

The difference in height between a person carrying two copies of the variant and a person carrying no copies is just under 1 cm in height, so does not on its own explain the range of heights across the population. However, the researchers believe the findings may prove important.

Previous studies have suggested that, unlike conditions such as obesity, which is caused by a mix of genetic and environmental factors (so called 'nature and nurture'), 90 per cent of normal variation in human height is due to genetic factors rather than, for example, diet. However, other than very rare gene variants that affect height in only a small number of people, no common gene variants have until now been identified.

The research was led by Dr Tim Frayling from the Peninsula Medical School, Exeter, Professor Mark McCarthy from the University of Oxford and Dr Joel Hirschhorn from the Broad Institute of Harvard and MIT in Cambridge, USA. Dr Frayling and Professor McCarthy were also part of a Wellcome Trust-funded study team that discovered the first common gene linked to obesity in April this year.

Using data from the Wellcome Trust Case Control Consortium - the largest study ever undertaken into the genetics underlying common diseases - and the Diabetes Genetics Initiative in the US, the researchers conducted a genome-wide study of DNA samples from 5000 people. The findings – that variations in the gene HMGA2 make some people taller than others – are published online today in the journal 'Nature Genetics'.

Each of us carries two copies of each gene, one from our mother and one from our father. However, each copy can be a variant, or allele – in the case of the HMGA2 gene, a 'tall' version and a 'short' version. The researchers found that as many as 25 per cent of white Europeans carried two 'tall' versions of this particular gene, making them approximately 1 cm taller than the 25 per cent of people who carry two 'short' versions.

"Height is a typical 'polygenic trait' – in other words, many genes contribute towards making us taller or shorter," explains Dr Frayling. "Clearly, our results do not explain why one person will be 6'5" and another only 4'10". This is just the first of many that will be found – possibly as many as several hundred."

The exact role that HMGA2 has in growth is unclear, but the researchers believe it is most likely in increased cell production. This may have implications for the development of cancer as tumours occur due to unregulated cell growth. Previous studies have shown an association between height and certain cancers: taller people are statistically more likely to be at risk from cancers, including those found in the prostate, bladder and lung.

"There appears to be a definite correlation between height and some diseases," explains Dr Mike Weedon, lead author on the study. "For example, there are associations between shortness and slightly increased risks of conditions such as heart disease. Similarly, tall people are more at risk from certain cancers and possibly osteoporosis."

Dr Frayling believes that the study has major implications for helping scientists understand how common variations in DNA in the human genome actually affect us, especially in relation to growth and development.

"Even though improved nutrition means that each generation is getting successively taller, variation in height within a population is almost entirely influenced by our genes," says Dr Frayling. "This fact, coupled with the ease of measuring height, means that height can act as a model trait, allowing us to explore in detail the influence that the genome actually has on our general make-up, not just disease risk."

In addition to being a textbook example of a complex trait, height is a common reason children are referred to specialists. Although short stature by itself typically does not signify cause for concern, delayed growth can sometimes reflect a more serious underlying medical condition.

"By defining the genes that normally affect stature, we might someday be able to better reassure parents that their child's height is within the range predicted by their genes, rather than a consequence of disease," said Dr Hirschhorn from the Broad Institute of Harvard and MIT.

The research was funded by the Wellcome Trust with support from Diabetes UK, the Medical Research Council and a number of additional funders.

Contact

Craig Brierley
Media Officer
Wellcome Trust
T +44 (0)20 7611 7329
E c.brierley@wellcome.ac.uk

Notes for editors

1. Weedon, M. et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genetics, 2 Sept 2007, e-pub ahead of print.

2. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

3. Diabetes UK is the charity for people with diabetes, their family friends and carers. Its mission is to improve the lives of people with the condition and work towards a future without diabetes by funding research, campaigning and helping people live with the condition. For more information, please call Sarah Milsom in the press office on 020 7424 1164. People can call the Diabetes UK Careline on 0845 120 2960 for further support and information about diabetes.

4. The Medical Research Council (MRC) is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public's needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world.

5. The Peninsula Medical School is a partnership between the Universities of Exeter and Plymouth and the NHS within Devon and Cornwall. Established in 2000, the school is involved in research in many areas of medicine; however, it has a particular interest in diabetes and has many internationally recognised research groups. Professor Andrew Hattersley's team at the Diabetes Genetics Centre was awarded the Queen's Anniversary Prize in 2006 for their pioneering work in genetic diabetes in children and young adults.

6. Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University's income and expenditure, and two-thirds of its external research income. Oxford's world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.

7. The Broad Institute of Harvard and MIT was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease.

The Institute is a research collaboration that involves faculty, professional staff and students from throughout the Harvard and MIT academic and medical communities. It is jointly governed by the two universities. Organised around Scientific Programs and Scientific Platforms, the unique structure of the Broad Institute enables scientists to collaborate on transformative projects across many scientific and medical disciplines.