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Epidemiology and Population Health

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

International Journal of Obesity volume 43, pages 2491–2499 (2019)Cite this article

Subjects

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.

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Acknowledgements

This project was supported by the EFSD/CDS/Lilly Collaborative Diabetes Research Program (2013), the Lundbeck Foundation [grant number R170-2014-1353]; the DFF research project 1 from the Danish Council for Independent Research, Medical Sciences (DFF-FSS): DFF–6110-00114; the Novo Nordisk Foundation Medical and Natural Sciences Research Grant [grant number NNF13OC0007493, and by the National Natural Science Foundation of China grant # 81773506.

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Authors and Affiliations

  1. Epidemiology and Biostatistics, Department of Public Health, University of Southern Denmark, Odense, Denmark

    Weilong Li, Afsaneh Mohammadnejad, Jesper Lund, Lene Christiansen & Qihua Tan

  2. Division of Epidemiology and Health Statistics, Qingdao University Medical College, Qingdao, China

    Dongfeng Zhang, Weijing Wang & Yili Wu

  3. Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Munich, Germany

    Jan Baumbach

  4. Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark

    Jan Baumbach

  5. Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Lene Christiansen

  6. Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Qihua Tan

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Li, W., Zhang, D., Wang, W. et al. DNA methylome profiling in identical twin pairs discordant for body mass index. Int J Obes 43, 2491–2499 (2019). https://doi.org/10.1038/s41366-019-0382-4

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