Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence
Lavinia Gordon, Jihoon E Joo, Joseph E Powel, Miina Ollikainen, Boris Novakovic, Xin Li, Roberta Andronikos, Mark N Cruickshank, Karen N Conneely, Alicia K Smith, Reid S Alisch, Ruth Morley, Peter M Visscher, Jeffrey M Craig, Richard Saffery
GENOME RESEARCH | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2012
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-pair methylation 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 ..View full abstract
Awarded by Australian National Health and Medical Research Council
Awarded by Bonnie Babes Foundation
Awarded by Financial Markets Foundation for Children
We thank the following people for kindly sharing their unpublished data: Robert Lyle and Kristina Gervin, Department of Medical Genetics, Oslo University Hospital and University of Oslo, Norway; Jennifer Harris, Division of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 Mcllroy, 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. Kiln, 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. Approved researchers can obtain the SSC population data set described in this study by applying at https://base.sfari.org. 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.