International study gives new insights into development in womb

An international study, involving scientists at the University of Southampton, has used an analysis of epigenetic marks on De-oxyribonucleic acid ( DNA) to measure how much a baby's development in the womb is determined by the genes inherited from the parents, as compared with the mother's nutrition, mental health and lifestyle.

The study, published in Genome Research, used samples of umbilical cord tissue DNA that were taken from 237 individuals (131 Chinese, 72 Malay, 34 Indian) in the Singapore GUSTO Birth Cohort Study. The baby's epigenetic profile was determined using infinium array technology and a million potential inherited genetic polymorphisms were measured.

Subsequent analysis, conducted by researchers at the National University of Singapore with Professor Keith Godfrey and Dr Sheila Barton of the Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, used 39 competing statistical models of genetic polymorphism alone, prenatal environment alone, and genetic differences interacting with the prenatal environment.

The results showed that genetic differences alone best explained 25 per cent of the epigenetic variation between babies, with the remaining 75 per cent best explained by the interaction of genetic differences and the prenatal environment.

Epigenetics refers to the complex set of reactions that control the development and maintenance of plants and animals by switching parts of the DNA on and off at strategic times and locations.

Professor Godfrey comments: "Development in the womb can in some ways be likened to an orchestra, in which genes are the instruments and epigenetic changes are the musicians who determine the sound that is heard, or the baby that is formed.

"Given the lasting health implications of development in the womb, this is an extremely important study; it is the world's first study using DNA itself to estimate how big a role the prenatal environment plays in a child's development and how much is simply genetically determined.

"Epigenetics, and in particular DNA methylation marks, are thought to link a baby's development in the womb with its risk of obesity and heart disease in later life. This research provides important new evidence that fixed changes in a baby's genes have only a modest influence on its epigenetic profile at birth and that most of the variation between babies arises from interactions between the environment experienced in the womb and the genetic information inherited from the parents.

"This has fundamental implications for how epigenetic studies will be conducted in the future and for our understanding of how the mother's nutrition and lifestyle have long-lasting effects on the health of her children."

The study was led by researchers at A*STAR's Singapore Institute for Clinical Sciences (SICS) in collaboration with the Yong Loo Lin School of Medicine, National University Health System, KK Women's and Children's Hospital.

They say that future studies on human epigenetic variation should include an assessment of the degree to which environmental influences are moderated by genetic differences.

Associate Professor Chong Yap Seng, GUSTO Lead Investigator and Acting Executive Director at SICS says: "These findings are likely to revolutionise our understanding of gene-environment interactions in early life and demonstrate the type of science that can be brought to bear when clinicians, basic scientists, and bioinformaticians work together."

Dr. Joanna Holbrook, corresponding author, adds: "The GUSTO birth cohort is an extremely powerful dataset to investigate how our experiences at the very beginnings of our lifetimes, in combination with our genes, affect our health throughout our lives. We see those messages transmitted via our DNA. We are asking fundamental questions about how the product of human evolution (our genes) interact with the individual circumstances we are born into, to shape our wellbeing.