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Author Notes:

Correspondening author Email: jeff.craig@mcri.edu.au

Jeffrey M. Craig and Richard Saffery contributed equally to this work.

We thank the following people for kindly sharing their unpublished data: Robert Lyle and Kristina Gervin, Department of Medical Genetics, Oslo University Hospital and University of Oslo, Norway; Jennifer Harris, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Jordana Bell and Pei-Chien Tsai, Department of Twin Research and Genetic Epidemiology, King's College and St. Thomas' Hospital, London, England; and Jonathan Mill and Chloe Wong, King's College, London, England.

We also thank John Carlin for his contributions to establishing the PETS cohort and for biostatistical support; obstetricians Mark Umstad, Royal Women's Hospital, Melbourne; Euan Wallace, Monash Medical Centre, Melbourne; and Mark Permezel, Mercy Hospital for Women, Melbourne for their contributions to establishing the PETS cohort and access to study participants; Sarah Healy, Tina Vaiano, Nicole Brooks, Jennifer Foord, Sheila Holland, Anne Krastev, Siva Illancheran, and Joanne Mockler for recruitment and sample collection; and Technical Officer Anna Czajko, Study Coordinator Geraldine McIlroy, and all mothers and twins that participated in this study.

Finally, we are grateful to all of the families at the participating SFARI Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, E. Wijsman).

We also appreciate the access to phenotypic data on SFARI Base.

Subjects:

Research Funding:

This work was supported by grants from the Australian National Health and Medical Research Council (grant numbers 437015 and 607358 to J.C. and R.S.), the Bonnie Babes Foundation (grant number BBF20704 to E.J.), the Sigrid Juselius Foundation (to M.O.), the Academy of Finland (to M.O.), the Finnish Cultural Foundation (to M.O.), the Financial Markets Foundation for Children (grant no. 032-2007), and by the Victorian Government's Operational Infrastructure Support Program.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biotechnology & Applied Microbiology
  • Genetics & Heredity
  • BIOCHEMISTRY & MOLECULAR BIOLOGY
  • BIOTECHNOLOGY & APPLIED MICROBIOLOGY
  • GENETICS & HEREDITY
  • ALLELE-SPECIFIC METHYLATION
  • CPG ISLAND SHORES
  • MONOZYGOTIC TWINS
  • BIRTH-WEIGHT
  • HUMAN GENOME
  • ADULT DISEASE
  • FETAL ORIGINS
  • EPIGENETIC EPIDEMIOLOGY
  • DEVELOPMENTAL ORIGINS
  • WIDE ASSOCIATION

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

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Journal Title:

Genome Research

Volume:

Volume 22, Number 8

Publisher:

, Pages 1395-1406

Type of Work:

Article | Final Publisher PDF

Abstract:

Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs.Within-pairmethylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

Copyright information:

© 2012, Published by Cold Spring Harbor Laboratory Press

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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