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Epidemiology and Population Health

Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity

International Journal of Obesity volume 48, pages 324–329 (2024)Cite this article

Subjects

Abstract

Background

Both genetic and epigenetic variations of GLP1R influence the development and progression of obesity. However, the underlying mechanism remains elusive. This study aims to explore the mediation roles of obesity-related methylation sites in GLP1R gene variants-obesity association.

Methods

A total of 300 Chinese adult participants were included in this study and classified into two groups: 180 metabolically healthy obesity (MHO) cases and 120 metabolically healthy normal-weight (MHNW) controls. Questionnaire investigation, physical measurement and laboratory examination were assessed in all participants. 18 single nucleotide polymorphisms (SNPs) and 31 CpG sites were selected for genotype and methylation assays. Causal inference test (CIT) was performed to evaluate the associations between GLP1R genetic variation, DNA methylation and MHO.

Results

The study found that rs4714211 polymorphism of GLP1R gene was significantly associated with MHO. Additionally, methylation sites in the intronic region of GLP1R (GLP1R−68-CpG 7.8.9; GLP1R−68-CpG 12.13; GLP1R−68-CpG 17; GLP1R−68-CpG 21) were associated with MHO, and two of these methylation sites (GLP1R−68-CpG 7.8.9; GLP1R−68-CpG 17) partially mediated the association between genotypes and MHO.

Conclusions

Not only the gene polymorphism, but also the DNA methylation of GLP1R was associated with MHO. Epigenetic changes in the methylome may in part explain the relationship between genetic variants and MHO.

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Fig. 1: Mediating effects of DNA methylation in the association between GLP1R polymorphisms and MHO.

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Data availability

The data generated and/or analyzed in the current study is available from the corresponding author upon 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

Funding

This study was supported by National Natural Science Foundation of China [grant number: 81773506].

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Authors and Affiliations

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

    Fulei Han, Shuai Zhu, Xiangjie Kong, Weijing Wang & Yili Wu

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  1. Fulei Han
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Contributions

FH and YW designed the study and wrote the manuscript. SZ and XK preprocessed the data. FH and WW performed the data analysis. YW reviewed the manuscript. All authors edited the final article. YW is the guarantor of this work and, has full access to all the data in the study.

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Correspondence to Yili Wu.

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Han, F., Zhu, S., Kong, X. et al. Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity. Int J Obes 48, 324–329 (2024). https://doi.org/10.1038/s41366-023-01414-1

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