NATURE AND NURTURE: BABY’S DEVELOPMENT IS AFFECTED BY GENES AND CONDITIONS IN THE WOMB
A*STAR-led international study provides new insights into the relationship between genes and prenatal environment
A recent study led by A*STAR’s Singapore Institute for Clinical Sciences (SICS) found that genetics as well as the environment in the womb play important roles in the development of the baby. The effort by the international team of scientists and clinicians is the world’s first attempt to discover how genetic and environmental factors affect the human epigenome. The results have fundamental implications for how epigenetic studies will be conducted in the future and for our understanding of how the mother’s nutrition and lifestyle may have long-lasting effects on the health of her children.
In this study, samples of umbilical cord tissue were taken from 237 individuals in the GUSTO Birth Cohort Study and their epigenetic profiles were examined. While genetic differences alone accounted for 25% of epigenetic variation, up to 75% could be attributed to interaction between genetic differences and prenatal environments. This means that both prenatal and genetic factors closely related.
Earlier research has shown that some of prenatal factors such as maternal smoking, maternal depression, maternal weight, infant birth weight, gestational age and birth order affect the development of foetuses. This study shows that the most variable epigenetic marks among new-borns are most likely to be driven by a combination of genetic differences and the environment in which the baby develops before birth. Thus, future studies on human epigenetic variation could include an assessment of how much environmental influences are affected by genetic differences. The findings were published in the respected genome biology and genomic medical journal Genome Research.
Coordinated by Senior Principal Investigator, Dr. Joanna Holbrook at A*STAR’s SICS, and in collaboration with the Yong Loo Lin School of Medicine, National University Health System, KK Women’s and Children’s Hospital, and overseas partners in Canada, U.K., and New Zealand, samples from the GUSTO Birth Cohort Study (detailed in Annex A) were used for this landmark study on Asian epigenetics.
“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 well-being,” remarked Dr Joanna Holbrook.
“These findings are likely to revolutionise our understanding of gene-environment interactions in early life and demonstrates the type of science that can be brought to bear when clinicians, basic scientists, and bio-informaticians work together,” said Associate Professor Chong Yap Seng, GUSTO Lead Investigator and Acting Executive Director at SICS.
Professor Keith Godfrey, Professor of Epidemiology and Human development at the Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, iterated, “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."
Notes to Editor:
The research findings described in this media release can be found in the Genome Research Journal, under the title, “A*STAR Research Made Great Discoveries” by Ai Ling Teh* 1 , Hong Pan* 1,2 , Li Chen 1 , Mei-Lyn Ong 1 , Shaillay Dogra 1 , Johnny Wong 1 , Julia L MacIsaac 3 , Sarah M Mah 3 , Lisa M McEwen 3 , Seang-Mei Saw 4 , Keith M Godfrey 5 , Yap-Seng Chong 1,6 , Kenneth Kwek 7 , Chee-Keong Kwoh 2 , Shu-E Soh 4,6 , Mary FF Chong 1,6 , Sheila Barton 5 , Neerja Karnani 1 , Clara Y Cheong 1 , Jan Paul Buschdorf 1 , Walter Stunkel 1 , Michael S Kobor 3 , Michael J Meaney 1,8 , Peter D Gluckman 1,9 , Joanna D Holbrook 1† *These authors contributed equally
1 Singapore Institute of Clinical sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore
2 School of Computer Engineering, Nanyang Technology University (NTU), Singapore
3 Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Canada
4 Saw Swee Hock School of Public Health, NUS, Singapore
5 MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, UK
6 Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore
7 KK Women's and Children's Hospital, Singapore
8 Ludmer Centre for Neuroinformatics and Mental Health, Douglas University Mental Health Institute, McGill University, Montreal Canada
9 Centre for Human Evolution, Adaptation and disease, Liggins Institute, University of Auckland
Correspondence should be addressed to
Joanna D Holbrook
Singapore Institute for Clinical Sciences
A*STAR, Brenner Centre for Molecular Medicine
30 Medical Drive, Singapore, 117609.
Full text of the paper can be accessed online here.
Annex A - About GUSTO Birth Cohort Study
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A*STAR Singapore Institute for Clinical Sciences
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About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners.
For more information about A*STAR, please visit www.a-star.edu.sg.
About the Singapore Institute for Clinical Sciences (SICS)
Established in 2007, the Singapore Institute for Clinical Sciences (SICS) is a research institute within the Agency for Science, Technology and Research (A*STAR), and its mission is to develop disease-oriented clinical and translational research programmes in key disease areas.
SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The clinical scientists in SICS conduct the full spectrum of “bench to bedside” research activities in metabolic diseases (including diabetes, obesity and insulin resistance), pathways to normal growth and development (including cognitive and behavioural development), nutritional sciences as well as in certain viral infectious diseases such as chronic viral diseases.
The institute aims to attract, train and nurture clinician-scientists and to develop joint programs with universities, academic medical centres, government hospitals and research institutes.
For more information on SICS, please visit: www.sics.a-star.edu.sg.
ANNEX A - ABOUT GUSTO BIRTH COHORT STUDY
Incepted in 2009 as a collaborative effort with the two major public maternity hospitals in Singapore, National University Health System (NUHS) and the KK Women’s & Children’s Hospital (KKH), GUSTO is the region’s leading longitudinal birth cohort study that combines multi-ethnic Asian participants with detailed records of ante and post-natal data and biological specimens from both mother and child. These data include rare insights into newborn body composition and correlated future obesity via infant MRIs in the 1st week of birth, molecular analysis of birth tissues (placenta, umbilical cord, cord blood) and ongoing breast milk, stool, nasal and buccal swab specimens post-natal up to 2 years of age for the over 1200 mother-child pairs recruited. [Clinical/experimental] assessments include nutritional, biochemical, imaging, molecular and cognitive studies of the mothers and infants, with extensive implications for understanding future metabolic compromise, allergic and respiratory illnesses, cognitive spectrum childhood disorders and more. Additional information on the GUSTO study is available online here.