CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Department of Endocrinology and Metabolism, Zhongshan Hospital and Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China.
Clin Epigenetics. 2024 May 27;16(1):70. doi: 10.1186/s13148-024-01679-x.
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.
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.
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.
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.
肥胖是一个全球性的公共卫生问题，与心血管疾病和 2 型糖尿病（T2D）等慢性病有关。新出现的证据表明，表观遗传修饰，特别是 DNA 甲基化，可能与肥胖有关。然而，BMI 纵向变化的分子机制尚未得到充分探索，特别是在东亚人群中。
本研究对两个中国队列的 533 名个体进行了长达四年的重复 DNA 甲基化和 BMI 测量的纵向全基因组关联分析，以发现与 BMI 变化相关的新型 DNA 甲基化位点。
我们确定了三个与 BMI 变化显著相关的新型 CpG 位点（cg14671384、cg25540824 和 cg10848724）。鉴定出的两个 CpG 位点位于先前与体型和基础代谢率相关的区域。对前 20 个 BMI 变化相关 CpG 进行注释，发现它们与肥胖和 T2D 密切相关。值得注意的是，这些 CpG 具有活跃的调节作用，位于肝脏和消化道中高表达的基因中，这表明通过 DNA 甲基化从基因组到能量代谢和吸收表型的潜在调节途径。横断面和纵向 EWAS 比较表明，与 BMI 和 BMI 变化相关的 CpG 之间存在不同的机制。
本研究增强了我们对 BMI 变化背后的表观遗传动态的理解，并强调了纵向分析在揭示表观遗传学和肥胖之间复杂相互作用方面的价值。
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