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Genetics and Epigenetics

An epigenome-wide association study of waist circumference in Chinese monozygotic twins

International Journal of Obesity (2024)Cite this article

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Abstract

Objectives

Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships.

Methods

A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage.

Results

We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites.

Conclusions

Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

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Fig. 1: Circular Manhattan plot for epigenome-wide association study of WC.
Fig. 2: Differential methylation patterns for the identified DMRs.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors appreciate the local Health Bureau, local Center for Disease Control and Prevention, other relevant governments and persons, investigators, and respondents for their support to this research.

Funding

This work was supported by the National Natural Science Foundation of China (grant number 81773506) and the Natural Science Foundation of Shandong Province (grant number ZR2023MH374).

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Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, Public Health College, Qingdao University, Qingdao, China

    Fangjie Xing, Fulei Han, Yan Wu, Bosen Lv, Weijing Wang, Dongfeng Zhang & Yili Wu

  2. Zhonglou District Center for Disease Control and Prevention, Changzhou, Jiangsu, China

    Huimin Tian

  3. Qingdao Municipal Center for Disease Control and Prevention, Qingdao, Shandong, China

    Xiaocao Tian, Chunsheng Xu & Haiping Duan

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  1. Fangjie Xing
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Contributions

FX participated to data analysis and wrote the manuscript. FH participated to data analysis. YW participated to data curation. BL participated to data curation. HT assisted in reviewing and revising the manuscript. WW participated in the visualization. XT participated to the investigation process. CX coordinated the planning of research activities. HD participated to the investigation process. DZ participated to data collection. YW designed the study and managed the execution of research activities. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Yili Wu.

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The authors declare no competing interests.

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This research was approved by Regional Ethics Committee of the Qingdao CDC Institutional Review Boards (QDCDC- IRB) and carried out in compliance with the guidelines of the Helsinki Declaration. Informed written consent was obtained from all individual participants included in the study.

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Xing, F., Han, F., Wu, Y. et al. An epigenome-wide association study of waist circumference in Chinese monozygotic twins. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01538-y

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