Gene links lower birth weight and type 2 diabetes

Gene links lower birth weight and type 2 diabetes

Two gene regions that influence a baby’s weight at birth have been identified by a large international team of researchers, including scientists from Oxford University. One of the genes is also associated with type 2 diabetes, which helps to explain why small babies have higher rates of diabetes in later life.

The team, with funding from the Wellcome Trust, Netherlands Organisation for Scientific Research, European Union, Medical Research Council, Academy of Finland and the US National Institutes of Health, analyzed the genomes of over 38,000 Europeans from 19 studies of pregnancy and birth.

Two genetic variants showed strong associations with birth weight. One of the variants, in a gene called ADCY5, has recently been linked with susceptibility to type 2 diabetes. Individuals who inherit two risk copies of this variant are at a 25 per cent higher risk of diabetes in adulthood than those who inherit two non-risk copies.

This is a key finding because it has long been known that babies that weigh less are more at risk of type 2 diabetes in adulthood, but it was not clear why. Much research has focused on the role of the womb environment. It is widely believed that the mother’s nutrition can influence both the growth of the baby and its later risk of disease, a process known as ‘programming’. However, this latest research confirms that genes are also important.

‘It was a surprise to see such strong genetic effects for a characteristic, such as birth weight, which is subject to powerful influences from so many environmental factors,’ said Professor Mark McCarthy of the Wellcome Trust Centre for Human Genetics at Oxford University, who was one of the leaders of the research. ‘These discoveries provide important clues to the mechanisms responsible for the control of growth in early life and may lead us to a better understanding of how to manage growth problems during pregnancy.’

The combined effects of the two identified gene regions are quite substantial. Nine per cent of Europeans inherit two copies of a genetic variant in each region and are, on average, 113g lighter at birth than the 24per cent who inherit one or no copies. This effect is equivalent to the reduction in birth weight caused by a mother smoking four to five cigarettes per day in pregnancy.

Dr. Rachel Freathy, Sir Henry Wellcome Postdoctoral Fellow at the Peninsula Medical School in Exeter, commented: ‘Our study shows that genes are part of the reason why babies born with a lower birth weight are more at risk of type 2 diabetes 50 or 60 years later. It is important for us now to establish how much of the association is due to our genes and how much is due to the environment because this will inform how we target efforts to prevent the disease.’

Professor Marjo-Riitta Jarvelin of Imperial College London, another of the leaders of the research, said: ‘We have, for nearly two decades, tried to discover the factors which may explain why smaller foetal size associates with so many later life chronic conditions such as heart disease. We have known for a long time that foetal growth is genetically influenced on the basis of family and other population studies, but the question has been where these markers are hiding? Also our own studies have demonstrated that a number of environmental factors influence foetal growth and that some foetuses are more vulnerable to those than the others. I believe that our genetic landmark discoveries will give us opportunity to answer these puzzling questions in the near future.’

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