Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs

Mubo Chen, Jan Baumbach, Fabio Vandin, Richard Röttger, Eudes Guilherme Vieira Barbosa, Mingchui Dong, Morten Frost Munk Nielsen, Lene Christiansen, Qihua Tan

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus “programming” the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such “programming” effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth-weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health.
Original languageEnglish
JournalAnnals of Human Genetics
Volume80
Issue number2
Pages (from-to)81-87
ISSN0003-4800
DOIs
Publication statusPublished - 2016

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DNA Methylation
Epigenomics
Monozygotic Twins
Chromosomes, Human, Pair 1
Health
Growth

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title = "Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs",
abstract = "Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus “programming” the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such “programming” effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth-weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health.",
author = "Mubo Chen and Jan Baumbach and Fabio Vandin and Richard R{\"o}ttger and {Vieira Barbosa}, {Eudes Guilherme} and Mingchui Dong and Nielsen, {Morten Frost Munk} and Lene Christiansen and Qihua Tan",
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Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs. / Chen, Mubo; Baumbach, Jan; Vandin, Fabio; Röttger, Richard; Vieira Barbosa, Eudes Guilherme; Dong, Mingchui; Nielsen, Morten Frost Munk; Christiansen, Lene; Tan, Qihua.

In: Annals of Human Genetics, Vol. 80, No. 2, 2016, p. 81-87.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs

AU - Chen, Mubo

AU - Baumbach, Jan

AU - Vandin, Fabio

AU - Röttger, Richard

AU - Vieira Barbosa, Eudes Guilherme

AU - Dong, Mingchui

AU - Nielsen, Morten Frost Munk

AU - Christiansen, Lene

AU - Tan, Qihua

PY - 2016

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N2 - Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus “programming” the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such “programming” effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth-weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health.

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