Epigenetic marks lay foundations for a child’s future abilities

Although it is now widely recognised that a poor start to life has long-term effects on a child’s later ability to learn, the mechanisms by which the environment in early life affects later life chances are poorly understood.

Research published today in the International Journal of Epidemiology provides new evidence that so-called ‘epigenetic processes’ influence brain development to have an important influence on a child’s later ability to learn and their cognitive performance. The study was led by University of Southampton researchers with teams from New Zealand and Singapore.

Epigenetic marks on our DNA account for how all cells in the body have the same DNA sequence, inherited from our parents, but nonetheless there are hundreds of different cell types. The body uses epigenetics as its principal control system, to increase or decrease the expression of our genes, and epigenetic processes are known to be important in memory and other aspects of brain function.

The new research used umbilical cord tissue collected at birth and identified epigenetic marks in a key brain development gene called HES1 that were linked to the child’s ability to learn and their cognitive performance at ages 4 and 7 years. The findings in two groups of children in Southampton, UK, were accompanied by additional findings in children from Singapore that HES1 epigenetic marks at birth were associated with aspects of socially disruptive behaviour that have previously been linked with a reduced school performance.

Professor Karen Lillycrop and Dr Paula Costello who led the research explained “Alongside the findings in different groups of children in the UK and Singapore we also found evidence for an effect of the epigenetic marks on the function of the HES1 gene in laboratory studies. Together, the findings provide substantial support for a role for epigenetics in mediating the long-term consequences of the early life environment on brain development and later cognitive performance.”

Professor Keith Godfrey, a member of the research team from the Medical Research Council Lifecourse Epidemiology Unit at the University of Southampton comments “To date the main focus of research to identify what determines a child’s ability to learn has been on influences acting after birth. The strong links between epigenetic marks at birth and a child’s ability to learn point to a much greater influence of brain development before birth than previously recognised. Research is now making progress in defining how the mother’s lifestyle and emotional wellbeing during pregnancy can alter epigenetic processes in the baby before birth – in time this could lead to new approaches to diminish disparities in later school performance.”

Dr Anne Rifkin-Graboi, Head of the Neurodevelopment Research Centre at A*STAR’s Singapore Institute of Clinical Sciences and a key investigator in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study included in the research adds, “This is the first time that epigenetic marks at birth have been linked with substantial effects on a child’s ability to learn. The effects on later cognitive function and behaviour in two culturally diverse populations are particularly noteworthy as they relate to healthy children within the normal range of size at birth. The research marks an important step forward in determining biological mechanisms through which brain development is susceptible to environmental exposures.”

The research teams are part of the EpiGen global research consortium, involving the Institute of Developmental Sciences, Centre for Biological Sciences and Medical Research Council Lifecourse Epidemiology Unit at the University of Southampton, the National University of Singapore, A*STAR’s Singapore Institute for Clinical Sciences and the Liggins Institute of the University of Auckland.


Notes for editors

1. The paper Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour, DOI 10.1093/ije/dyv052 is available upon request from the media relations team. Please contact Charles Elder, Media Relations Manager at the University of Southampton for a copy. 

2. The study was funded by grants from the UK Medical Research Council, British Heart Foundation, Arthritis Research UK, National Osteoporosis Society, International Osteoporosis Foundation, Cohen Trust, Gravida-National Research Centre for Growth and Development, Abbott Nutrition, National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford and National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Singapore National Research Foundation and Agency for Science Technology and Research.


About the EpiGen Consortium

EpiGen is a global consortium of leading researchers based at five centres in three countries (Auckland UniServices Limited, University of Southampton, Medical Research Council Lifecourse Epidemiology Unit - University of Southampton, Singapore Institute for Clinical Sciences of the Agency for Science, Technology and Research (A*STAR), and National University of Singapore).  EpiGen strives to advance understanding of the developmental and environmental processes that influence health through the life course.

For more information on the EpiGen Consortium, please visit http://www.epigengrc.com


About the University of Southampton

Through world-leading research and enterprise activities, the University of Southampton connects with businesses to create real-world solutions to global issues. Through its educational offering, it works with partners around the world to offer relevant, flexible education, which trains students for jobs not even thought of. This connectivity is what sets Southampton apart from the rest; we make connections and change the world. http://www.southampton.ac.uk/

For more information on the University of Southampton, please contact Mr. Charles Elder:  C.Elder@soton.ac.uk 


About the MRC Lifecourse Epidemiology Unit

The MRC Lifecourse Epidemiology Unit (LEU) was established in 2010, under the direction of Professor Cyrus Cooper, and addresses the environmental determinants of musculoskeletal and metabolic disease throughout the lifecourse.  In May 2013, the unit completed its integration with the University of Southampton in a successful University-Unit Partnership (UUP).  We are interested in the interplay of causes acting at different stages of the lifecourse from before conception through to old age, and the ways in which environmental influences modulate gene expression to produce disease. Through an understanding of the causes of these disorders, and evaluation of interventions at appropriate stages in the lifecourse, we aim to provide robust and timely evidence which informs policies to improve population and individual health. The unit has 75 staff and a budget of £3m per year.


About GUSTO

Incepted in 2009 as a collaborative effort with the two major public maternity hospitals in Singapore, KK Women’s & Children’s Hospital (KKH) and the National University Health System (NUHS), 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 new-born 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 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. This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council. Additional information on the GUSTO study is available online at http://gusto.sg.


About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. 
In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore’s manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. 
A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR’s research entities as well as a growing number of corporate laboratories. 
For more information on 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


About the KK Women's and Children's Hospital (KKH)

KK Women’s and Children’s Hospital (KKH) is a leading healthcare centre for Obstetrics, Gynaecology, Paediatrics and Neonatology. Founded in 1858, the 830-bed JCI accredited hospital is a referral centre providing tertiary services to manage complex conditions in women and children. More than 400 specialists adopt a multi-disciplinary and holistic approach to treatment, and harness the latest innovations and technology for the best medical care possible.
As an academic and research institution, KKH is a major teaching hospital for Duke-NUS Graduate Medical School, Yong Loo Lin School of Medicine and Lee Kong Chian School of Medicine. The hospital also runs the largest residency programmes for Obstetrics and Gynaecology and Paediatrics in Singapore, accredited by the Accreditation Council for Graduate Medical Education International (ACGME-I). 
For more information on KKH, please visit: www.kkh.com.sg.


About the National University Health System (NUHS) 

The National University Health System (NUHS) groups the National University Hospital (NUH), the NUS Yong Loo Lin School of Medicine, the NUS Faculty of Dentistry and the Saw Swee Hock School of Public Health under a common governance structure to create synergies to advance health by integrating clinical care, research and education. The enhanced capabilities and capacity will enable the NUHS to deliver better patient care, train future generations of doctors more effectively and bring innovative treatments to patients through groundbreaking research. 
For more information about the NUHS, please visit: www.nuhs.edu.sg.


About the Liggins Institute, University of Auckland

The Liggins Institute is a Large-Scale Research Institute of The University of Auckland, NZ. The Institute’s research demonstrates the importance of children having a healthy start to life and the ongoing role of nutrition in promoting and supporting optimal health throughout life. 
The multidisciplinary, translational research seeks to understand the biological mechanisms that drive critical processes during development and harness that knowledge in ways that will improve quality of life across communities and generations.
www.liggins.auckland.ac.nz