Longitudinal analysis of epigenome-wide DNA methylation reveals novel loci associated with BMI change in East Asians.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2024-05-27 DOI:10.1186/s13148-024-01679-x

Wenran Li, Mingfeng Xia, Hailuan Zeng, Huandong Lin, Andrew E Teschendorff, Xin Gao, Sijia Wang

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引用次数: 0

Abstract

Background: Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations.

Methods: This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years.

Results: We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change.

Conclusion: This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.

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对全表观基因组 DNA 甲基化的纵向分析揭示了与东亚人体重指数变化相关的新位点。

背景：肥胖症是与心血管疾病和 2 型糖尿病（T2D）等慢性疾病相关的全球公共卫生问题。新的证据表明，表观遗传修饰（尤其是 DNA 甲基化）可能是导致肥胖的原因之一。然而，BMI 纵向变化的分子机制尚未得到充分探讨，尤其是在东亚人群中：本研究对 DNA 甲基化进行了纵向全表观基因组关联分析，以发现与 BMI 变化相关的新位点：结果：我们发现了三个与 BMI 变化显著相关的新 CpG 位点（cg14671384、cg25540824 和 cg10848724）。其中发现的两个 CpG 位点位于以前与体形和基础代谢率相关的区域。对与 BMI 变化相关的前 20 个 CpGs 进行注释后发现，这些 CpGs 与肥胖和 T2D 密切相关。值得注意的是，这些CpGs表现出积极的调控作用，并且位于肝脏和消化道中高表达的基因中，这表明从基因组到能量代谢和吸收表型之间存在一条通过DNA甲基化的潜在调控途径。横向和纵向EWAS比较表明，与BMI相关的CpGs和BMI变化之间存在不同的机制：这项研究加深了我们对 BMI 变化背后的表观遗传动态的理解，并强调了纵向分析在解读表观遗传学与肥胖之间复杂的相互作用方面的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.