First common height gene identified by researchers behind 'obesity gene' finding

Sep 3 2007

Whilst 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 1cm 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% 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, US. 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 5,000 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% of white Europeans carried two "tall" versions of this particular gene, making them approximately 1cm taller than the 25% 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 the 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.