An international genetic study of more than 150,000 people, published today in Nature, has identified genetic differences that help to explain why some babies are born bigger or smaller than others.

The large-scale study reveals how these genetic differences provide an important link between an individual’s early growth and their chances of developing conditions such as type 2 diabetes or heart disease in later life,  and could help to identify new ways of preventing and treating these diseases.

The research concluded that a substantial proportion (at least one-sixth) of the variation in birth weight is down to genetic differences between babies. This is seven to eight times more variation than is explained by environmental factors already known to influence birth weight, such as whether the mother smokes during pregnancy or her body mass index (a measure of obesity).

Dr Rachel Freathy, a co-lead author at the University of Exeter Medical School, said:

This study has revealed how the small genetic differences between individuals can collectively have quite large effects on birth weight, and how those same genetic differences are often linked to poor health in later life. Weight at birth is influenced by many factors, including the baby’s genes and those of its parents, as well as by the nutrition made available and the environment provided by the mother. We now have a much more detailed view of the ways in which these genetic and environmental elements work together to influence early growth and later disease.”

It has been known for some time that individuals whose birthweight is below, or above, the average have a higher risk of diabetes when they are adults. Until now, many researchers have assumed that this link reflects the long-term impact of the nutritional environment in which the fetus develops: in other words, that events that alter nutrition in early life can “set up” an individual’s body in ways that make them more prone to disease in later life.

The researchers analysed genetic differences throughout the genomes of nearly 154,000 people from across the world. Around half of these came from the UK Biobank study, and Dr John Perry, a Senior Investigator from the MRC Epidemiology Unit at the University of Cambridge, and also a co-lead author on this research, said:

Our genetic studies involve close co-operation between investigators across many institutions around the world and have been hugely powerful in uncovering new insights into the biology of child growth and development and how this affects disease risks. UK Biobank is one of the largest health resources in the world and has hugely accelerated the pace of genetic and other research discoveries.”

By matching the genetic profiles of these people to information on birth weight, the researchers could identify sixty regions of the genome that were clearly driving differences in birthweight. They then analysed data from previous studies on diseases such as diabetes and heart disease, and found that many of the same genomic regions were implicated.

The researchers uncovered a substantial overlap between the genetic regions that explain differences in birth weight and those that confer higher risks of developing diabetes, high blood pressure or heart disease. This overlap is mostly seen in the baby’s genetic profile, but the team also found that the mother’s genes also play an important role in influencing her baby’s birth weight, most likely by altering the amount of nutrition that the mother makes available to the baby during pregnancy.

Professor Mark McCarthy, a co-lead author at the University of Oxford, said:

These findings provide vital clues to the some of the processes that act over decades of life to influence an individual’s chances of developing diabetes and heart disease. These should highlight new approaches to treatment and prevention. Understanding the contributions of all of these processes will also tell us how much we should expect the many, wonderful improvements in antenatal care to reduce the burden of future diabetes and heart disease”.

Dr Ken Ong, a Paediatrician and Group Leader from the MRC Epidemiology Unit at the University of Cambridge, and also a co-lead author on this research, said:

“For many years now, studies have been reported that birth weight can leave patterns of higher or lower risk for diabetes and heart disease in later life. But we have not understood why this happens and these findings have not informed health care. Some investigators have even questioned whether these risk patterns are real or are statistical artefacts. These findings now robustly show that many biological processes that increase birth weight also protect individuals from later diabetes and heart disease.”

The new study was jointly led by a team of researchers from six institutions including the universities of Exeter, Oxford, Bristol, Cambridge and Queensland, and the Erasmus Medical Centre in Rotterdam. The research involved more than 160 international researchers from 17 countries who are members of the Early Growth Genetics (EGG) Consortium. The work was supported by more than 120 research funders: the major sources of funding for UK researchers were the Wellcome Trust, the Royal Society, the Medical Research Council, the National Institute for Health Research and the European Union.

• Paper: Momoko Horikoshi, Robin N Beaumont, Felix R Day et al.  Genome-wide associations for birth weight and correlations with adult disease. Nature; 28 September 2016; DOI: 10.1038/nature19806