Genes link growth in the womb with adult metabolism and disease

Researchers have identified four new genetic regions that influence birth weight, providing further evidence that genes as well as maternal nutrition are important for growth in the womb. Three of the regions are also linked to adult metabolism, 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. Three genetic regions have already been identified that influence birth weight, two of which are also linked to an increased susceptibility to type 2 diabetes.

The latest study analysed almost 70 000 individuals of European, Arab, Asian and African-American descent from across 50 separate studies of pregnancy and birth. Their findings confirmed the three regions previously identified and also revealed four new genetic regions that are associated with birth weight. 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 Institutes of Health (USA).

One of the new genetic regions is also associated with blood pressure in adulthood, providing the first evidence of a genetic link between birth weight and blood pressure. Two of the regions are known to be linked to adult height, showing that genes involved in growth begin to take effect at a very early stage.

Professor Mark McCarthy, a co-author of the study from the Wellcome Trust Centre for Human Genetics at Oxford, said: “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. 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 about 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 and a Sir Henry Wellcome Postdoctoral Fellow 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.”

Together, the newly identified genetic regions have a surprisingly large effect on birth weight when compared with known environmental influences. Dr Inga Prokopenko, co-lead author from the University of Oxford, explained: “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.”

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

Struan F A Grant, associate director of the Center for Applied Genomics at the Children’s Hospital of Philadelphia and one of the study authors, 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.”

Reference

Horikoshi M et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet 2012. [epub].

Notes for editors

About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

About the University of Exeter
The Sunday Times University of the Year 2012-13, the University of Exeter is a Russell Group university and in the top 1 per cent of institutions globally. It combines world-class research with very high levels of student satisfaction. Exeter has over 18,000 students and is ranked seventh in the Sunday Times University Guide, tenth in the UK in the Times Good University Guide 2012 and tenth in the Guardian University Guide. In the 2008 Research Assessment Exercise, 90 per cent of the University’s research was rated as being at internationally recognised levels and 16 of its 31 subjects are ranked in the top ten, with 27 subjects ranked in the top 20.

The University has invested strategically to deliver more than £350 million worth of new facilities across its campuses for 2012, including landmark new student services centres - the Forum in Exeter and The Exchange in Cornwall - and world-class new facilities for biosciences, the Business School and the Environment and Sustainability Institute.

About the University of Oxford’s Medical Sciences Division
The University of Oxford’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2500 people involved in research and more than 2800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.

From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

About the Children’s Hospital of Philadelphia
The Children’s Hospital of Philadelphia was founded in 1855 as the first paediatric hospital in the United States. Through its long-standing commitment to providing exceptional patient care, training new generations of paediatric healthcare professionals and pioneering major research initiatives, the Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its paediatric research programme is among the largest in the nation, ranking third in National Institutes of Health funding. In addition, its unique family-centred care and public service programmes have brought the 516-bed hospital recognition as a leading advocate for children and adolescents.