Twin Research and Human Genetics

Articles

The Peri/Postnatal Epigenetic Twins Study (PETS)

Yuk Jing Lokea1, Boris Novakovica2a3, Miina Ollikainena4, Euan M. Wallacea5, Mark P. Umstada6, Michael Permezela7, Ruth Morleya1, Anne-Louise Ponsonbya8, Lavinia Gordona9, John C. Galatia10, Richard Safferya2a3 * and Jeffrey M. Craiga1 c1 *

a1 Department of Paediatrics, Early Life Epigenetics Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia

a2 Cancer and Disease Epigenetics Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia

a3 Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia

a4 Hjelt Institute, Department of Public Health, University of Helsinki, Finland

a5 The Ritchie Centre, Monash Institute of Medical Research, Melbourne, Australia

a6 Department of Obstetrics and Gynaecology (Royal Women's Hospital), University of Melbourne, Melbourne, Australia

a7 Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Melbourne, Australia

a8 Environmental & Genetic Epidemiology Research, Murdoch Childrens Research Institute, Melbourne, Australia

a9 Bioinformatics Unit, Murdoch Childrens Research Institute, Melbourne, Australia

a10 Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, Melbourne, Australia

Abstract

The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the individual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and samples of plasma and serum taken at 28 weeks’ gestation. We attended 75% of all births, at which time we collected multiple biological samples including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months; shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD.

(Received September 14 2012)

(Accepted October 12 2012)

(Online publication November 22 2012)

Keywords:

  • twins;
  • epigenetic;
  • birth;
  • developmental origins;
  • environment

Correspondence:

c1 address for correspondence: Dr. Jeffrey M. Craig, Early Life Epigenetics Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia. E-mail jeff.craig@mcri.edu.au

Footnotes

*  Contributed equally to this study.

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