Gene provides a link between lower birth weight and type 2 diabetes

New research uncovers two genetic regions that influence birth weight. One of the regions is also associated with type 2 diabetes, which helps to explain why small babies have higher rates of diabetes in later life.

A large international team of researchers, including scientists from several UK and international centres, has discovered two gene regions that affect a baby's size at birth. The research, published in 'Nature Genetics', is the first robust evidence that a well-known link between lower birth weight and susceptibility to type 2 diabetes has a genetic component.

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).

The team analysed 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 latest study shows that they also weigh less at birth.

This is a key finding because it has long been known that lower weight babies 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 her baby and its later risk of disease, a process known as 'programming'. However, this latest research confirms that genes are also important.

Dr Rachel Freathy, a Sir Henry Wellcome Postdoctoral Fellow at the Peninsula Medical School, 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 now important for us 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."

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 24 per cent who inherit one or no copy. This effect is equivalent to the birth weight reduction caused by a mother smoking four to five cigarettes per day in pregnancy.

Mark McCarthy from the University of Oxford who was one of the leaders of the research, said "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. 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".

Dorret Boomsma, Professor in the Department of Biological Psychology at Vrije University, Amsterdam, commented: "These findings illustrate that genetic research can help resolve the complex chain of causality underlying the association between early life course and later health outcomes."

Marjo-Riitta Jarvelin, Paediatrician and Professor in Lifecourse Epidemiology at Imperial College London and one of the leaders of the research, said: "We have, for nearly two decades, tried to discover the factors which may explain why smaller fetal size associates with so many later life chronic conditions such as heart disease. We have known for a long time that fetal 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 fetal growth and that some fetuses 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."

Notes for editors

About the Peninsula Medical School

The Peninsula Medical School is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West of England, and a partner of the Combined Universities in Cornwall. The Peninsula Medical School has created for itself an excellent national and international reputation for groundbreaking research in the areas of diabetes and obesity, neurological disease, child development and ageing, clinical education, health and the environment and health technology assessment. The Peninsula Medical School is licensed under the Human Tissue Act to hold ethically acquired human tissue.

About the Medical Sciences Division

University of Oxford's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of the University of Oxford'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.

About Imperial College London

Consistently rated among the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.

About the Netherlands Twin Register

The Netherlands Twin Register (NTR) follows new born and adult twins longitudinally since the late 1980's. Multiple assessments (up 10 to 12 times over 20 years) of health and behaviour are available in large groups of twins and their family members. In the NTR biobank, which collected biological samples including DNA, genotypic and phenotypic information is combined to aid in the detection of genetic variants influencing health and disease.

The Netherlands Twin Register has been established at the department of Biological Psychology at the VU University Amsterdam. VU University Amsterdam stands for high quality, fundamental, innovative and socially oriented research. The university has several leading research groups, all of which enjoy international recognition. In recent years, capacity and expertise have been pooled in large-scale programmes, enabling interactions between different disciplines to be exploited to the full.

About the Wellcome Trust

The Wellcome Trust is a global charity 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.