DNA methylome profiling in identical twin pairs discordant for body mass index

Weilong Li, Dongfeng Zhang, Weijing Wang, Yili Wu, Afsaneh Mohammadnejad, Jesper Lund, Jan Baumbach, Lene Christiansen, Qihua Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVE: Body mass index (BMI) serves as an important measurement of obesity and adiposity, which are highly correlated with cardiometabolic diseases. Although high heritability has been estimated, the identified genetic variants by genetic association studies only explain a small proportion of BMI variation. As an active effort for further exploring the molecular basis of BMI variation, large-scale epigenome-wide association studies have been conducted but with limited number of loci reported, perhaps due to poorly controlled confounding factors, including genetic factors. Being genetically identical, monozygotic twins discordant for BMI are ideal subjects for analyzing the epigenetic association between DNA methylation and BMI, providing perfect control on their genetic makeups largely responsible for BMI variation. SUBJECTS: We performed an epigenome-wide association study on BMI using 30 identical twin pairs (15 male and 15 female pairs) with age ranging from 39 to 72 years and degree of BMI discordance ranging from 3-7.5 kg/m2. Methylation data from whole blood samples were collected using the reduced representation bisulfite sequencing technique. RESULTS: After adjusting for blood cell composition and clinical variables, we identified 136 CpGs with p-value < 1e-4, 30 CpGs with p < 1e-05 but no CpGs reached genome-wide significance. Genomic region-based analysis found 11 differentially methylated regions harboring coding and non-coding genes some of which were validated by gene expression analysis on independent samples. CONCLUSIONS: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on BMI and obesity.
Original languageEnglish
JournalInternational Journal of Obesity
Number of pages9
ISSN0307-0565
DOIs
Publication statusE-pub ahead of print - 31. May 2019

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Monozygotic Twins
Body Mass Index
DNA Methylation
Epigenomics
Adiposity
Genetic Association Studies
DNA Sequence Analysis

Cite this

@article{997cd363482644bc8a0ac21f07cb0f71,
title = "DNA methylome profiling in identical twin pairs discordant for body mass index",
abstract = "OBJECTIVE: Body mass index (BMI) serves as an important measurement of obesity and adiposity, which are highly correlated with cardiometabolic diseases. Although high heritability has been estimated, the identified genetic variants by genetic association studies only explain a small proportion of BMI variation. As an active effort for further exploring the molecular basis of BMI variation, large-scale epigenome-wide association studies have been conducted but with limited number of loci reported, perhaps due to poorly controlled confounding factors, including genetic factors. Being genetically identical, monozygotic twins discordant for BMI are ideal subjects for analyzing the epigenetic association between DNA methylation and BMI, providing perfect control on their genetic makeups largely responsible for BMI variation. SUBJECTS: We performed an epigenome-wide association study on BMI using 30 identical twin pairs (15 male and 15 female pairs) with age ranging from 39 to 72 years and degree of BMI discordance ranging from 3-7.5 kg/m2. Methylation data from whole blood samples were collected using the reduced representation bisulfite sequencing technique. RESULTS: After adjusting for blood cell composition and clinical variables, we identified 136 CpGs with p-value < 1e-4, 30 CpGs with p < 1e-05 but no CpGs reached genome-wide significance. Genomic region-based analysis found 11 differentially methylated regions harboring coding and non-coding genes some of which were validated by gene expression analysis on independent samples. CONCLUSIONS: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on BMI and obesity.",
author = "Weilong Li and Dongfeng Zhang and Weijing Wang and Yili Wu and Afsaneh Mohammadnejad and Jesper Lund and Jan Baumbach and Lene Christiansen and Qihua Tan",
year = "2019",
month = "5",
day = "31",
doi = "10.1038/s41366-019-0382-4",
language = "English",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",

}

DNA methylome profiling in identical twin pairs discordant for body mass index. / Li, Weilong; Zhang, Dongfeng; Wang, Weijing ; Wu, Yili ; Mohammadnejad, Afsaneh; Lund, Jesper; Baumbach, Jan; Christiansen, Lene; Tan, Qihua.

In: International Journal of Obesity, 31.05.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - DNA methylome profiling in identical twin pairs discordant for body mass index

AU - Li, Weilong

AU - Zhang, Dongfeng

AU - Wang, Weijing

AU - Wu, Yili

AU - Mohammadnejad, Afsaneh

AU - Lund, Jesper

AU - Baumbach, Jan

AU - Christiansen, Lene

AU - Tan, Qihua

PY - 2019/5/31

Y1 - 2019/5/31

N2 - OBJECTIVE: Body mass index (BMI) serves as an important measurement of obesity and adiposity, which are highly correlated with cardiometabolic diseases. Although high heritability has been estimated, the identified genetic variants by genetic association studies only explain a small proportion of BMI variation. As an active effort for further exploring the molecular basis of BMI variation, large-scale epigenome-wide association studies have been conducted but with limited number of loci reported, perhaps due to poorly controlled confounding factors, including genetic factors. Being genetically identical, monozygotic twins discordant for BMI are ideal subjects for analyzing the epigenetic association between DNA methylation and BMI, providing perfect control on their genetic makeups largely responsible for BMI variation. SUBJECTS: We performed an epigenome-wide association study on BMI using 30 identical twin pairs (15 male and 15 female pairs) with age ranging from 39 to 72 years and degree of BMI discordance ranging from 3-7.5 kg/m2. Methylation data from whole blood samples were collected using the reduced representation bisulfite sequencing technique. RESULTS: After adjusting for blood cell composition and clinical variables, we identified 136 CpGs with p-value < 1e-4, 30 CpGs with p < 1e-05 but no CpGs reached genome-wide significance. Genomic region-based analysis found 11 differentially methylated regions harboring coding and non-coding genes some of which were validated by gene expression analysis on independent samples. CONCLUSIONS: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on BMI and obesity.

AB - OBJECTIVE: Body mass index (BMI) serves as an important measurement of obesity and adiposity, which are highly correlated with cardiometabolic diseases. Although high heritability has been estimated, the identified genetic variants by genetic association studies only explain a small proportion of BMI variation. As an active effort for further exploring the molecular basis of BMI variation, large-scale epigenome-wide association studies have been conducted but with limited number of loci reported, perhaps due to poorly controlled confounding factors, including genetic factors. Being genetically identical, monozygotic twins discordant for BMI are ideal subjects for analyzing the epigenetic association between DNA methylation and BMI, providing perfect control on their genetic makeups largely responsible for BMI variation. SUBJECTS: We performed an epigenome-wide association study on BMI using 30 identical twin pairs (15 male and 15 female pairs) with age ranging from 39 to 72 years and degree of BMI discordance ranging from 3-7.5 kg/m2. Methylation data from whole blood samples were collected using the reduced representation bisulfite sequencing technique. RESULTS: After adjusting for blood cell composition and clinical variables, we identified 136 CpGs with p-value < 1e-4, 30 CpGs with p < 1e-05 but no CpGs reached genome-wide significance. Genomic region-based analysis found 11 differentially methylated regions harboring coding and non-coding genes some of which were validated by gene expression analysis on independent samples. CONCLUSIONS: Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on BMI and obesity.

U2 - 10.1038/s41366-019-0382-4

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JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

ER -