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Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence
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 discord...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409253/ https://www.ncbi.nlm.nih.gov/pubmed/22800725 http://dx.doi.org/10.1101/gr.136598.111 |
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author | Gordon, Lavinia Joo, Jihoon E. Powell, Joseph E. Ollikainen, Miina Novakovic, Boris Li, Xin Andronikos, Roberta Cruickshank, Mark N. Conneely, Karen N. Smith, Alicia K. Alisch, Reid S. Morley, Ruth Visscher, Peter M. Craig, Jeffrey M. Saffery, Richard |
author_facet | Gordon, Lavinia Joo, Jihoon E. Powell, Joseph E. Ollikainen, Miina Novakovic, Boris Li, Xin Andronikos, Roberta Cruickshank, Mark N. Conneely, Karen N. Smith, Alicia K. Alisch, Reid S. Morley, Ruth Visscher, Peter M. Craig, Jeffrey M. Saffery, Richard |
author_sort | Gordon, Lavinia |
collection | PubMed |
description | 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 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. |
format | Online Article Text |
id | pubmed-3409253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34092532013-02-01 Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence Gordon, Lavinia Joo, Jihoon E. Powell, Joseph E. Ollikainen, Miina Novakovic, Boris Li, Xin Andronikos, Roberta Cruickshank, Mark N. Conneely, Karen N. Smith, Alicia K. Alisch, Reid S. Morley, Ruth Visscher, Peter M. Craig, Jeffrey M. Saffery, Richard Genome Res Research 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 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. Cold Spring Harbor Laboratory Press 2012-08 /pmc/articles/PMC3409253/ /pubmed/22800725 http://dx.doi.org/10.1101/gr.136598.111 Text en © 2012, Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/. |
spellingShingle | Research Gordon, Lavinia Joo, Jihoon E. Powell, Joseph E. Ollikainen, Miina Novakovic, Boris Li, Xin Andronikos, Roberta Cruickshank, Mark N. Conneely, Karen N. Smith, Alicia K. Alisch, Reid S. Morley, Ruth Visscher, Peter M. Craig, Jeffrey M. Saffery, Richard Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title | Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title_full | Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title_fullStr | Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title_full_unstemmed | Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title_short | Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
title_sort | neonatal dna methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409253/ https://www.ncbi.nlm.nih.gov/pubmed/22800725 http://dx.doi.org/10.1101/gr.136598.111 |
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