Genes link growth in the womb with diseases in adulthood

Four new genetic regions that influence babies' birth weight have been identified by an international research team involving the University of Oxford.

The findings provide further evidence that genes are important for growth in the womb, as well as the mother's nutrition. 

Together, the newly identified genetic regions have a surprisingly large effect on birth weight when compared with other known influences. 

'Birth weight is subject to powerful influences from many environmental factors. It was a surprise to see that the genetic effects, in combination, have a similar impact to that of maternal smoking in pregnancy, which itself is well known to lead to lower birth weight babies,' Dr Inga Prokopenko, co-lead author from the University of Oxford, explained.

Three of the gene regions identified are also linked to metabolism in adulthood, helping to explain why smaller babies have higher rates of chronic diseases later in life.

It has been known for some time that babies born with a lower birth weight are at higher risk of chronic diseases such as type 2 diabetes and cardiovascular disease. 

The international research team was led by scientists from the UK, Finland, the Netherlands and the United States. The team’s findings are published in the journal Nature Genetics

The study analysed the DNA of almost 70,000 individuals of European descent from across 43 separate studies of pregnancy and birth. The researchers revealed four new genetic regions that are associated with birth weight. 

One of the new regions is associated with blood pressure in adulthood, providing the first evidence of a genetic link between birth weight and blood pressure. 

Two of the gene regions are known to be linked to adult height, showing that genes involved in growth begin to take effect at a very early stage.

The research team also confirmed three genetic regions previously identified as influencing birth weight, two of which are known to be linked to increased susceptibility to type 2 diabetes. 

The study was funded by the Wellcome Trust, the Netherlands Organisation for Scientific Research, the European Union, the Medical Research Council (UK), the Academy of Finland and the National Institute of Health (USA).

'Our findings add to the growing evidence that events during early growth in the womb can have a significant impact on our health as adults,' said Professor Mark McCarthy, a co-author of the study from the Wellcome Trust Centre for Human Genetics at the University of Oxford. 'However, these genes tell only part of the story. It's important that we understand how much is down to genetics and how much is due to the environment in which we grow so that we can target efforts to prevent disease later in life.'

It's not clear how the genetic regions identified affect both birth weight and adult metabolism, although the findings do offer some clues as to the biological pathways involved. 

For example, the two genetic regions linking birth weight with type 2 diabetes risk are also associated with reduced levels of insulin. Insulin is the hormone responsible for regulating sugar levels in the blood, but it is also known to have an important role in early growth.  

Dr Rachel Freathy, co-lead author from the University of Exeter Medical School, said: 'These discoveries give us important clues to the mechanisms responsible for the control of a baby's growth in the womb, and may eventually lead to a better understanding of how to manage growth problems during pregnancy.'

Co-author Struan Grant, associate director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, said: 'This study demonstrates that genes acting early in development have important effects on health both in childhood and beyond. While we continue to learn more about the biology, an important implication is that designing prenatal interventions to improve birth weight could have lifelong health benefits.'