PDF(Pubmed)
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：肥胖是与心血管疾病和2型糖尿病（T2D）等慢性疾病有关的全球公共卫生问题。新出现的证据表明表观遗传修饰，特别是DNA甲基化，可能会导致肥胖。然而,BMI纵向变化的分子机制尚未得到很好的探索，特别是在东亚人群中。
方法：本研究进行了DNA甲基化的纵向表观全基因组关联分析，以发现与BMI变化相关的新基因座，来自两个中国队列中的533名个体，在四年内重复进行DNA甲基化和BMI测量。
结果：我们确定了三个新的CpG位点（cg14671384、cg25540824和cg10848724）与BMI变化显著相关。确定的CpG位点中的两个位于先前与身体形状和基础代谢率相关的区域中。前20名BMI变化相关CpG的注释显示与肥胖和T2D有很强的联系。值得注意的是,这些CpGs表现出积极的调节作用，并位于肝脏和消化道中高表达的基因中，提示从基因组到通过DNA甲基化的能量代谢和吸收表型的潜在调节途径。横截面和纵向EWAS比较表明CpG与BMI和BMI变化相关的不同机制。
结论：这项研究增强了我们对BMI变化的表观遗传动力学的理解，并强调了纵向分析在破译表观遗传学与肥胖之间复杂的相互作用方面的价值。
方法：本研究进行了DNA甲基化的纵向表观全基因组关联分析，以发现与BMI变化相关的新基因座，来自两个中国队列中的533名个体，在四年内重复进行DNA甲基化和BMI测量。
结果：我们确定了三个新的CpG位点（cg14671384、cg25540824和cg10848724）与BMI变化显著相关。确定的CpG位点中的两个位于先前与身体形状和基础代谢率相关的区域中。前20名BMI变化相关CpG的注释显示与肥胖和T2D有很强的联系。值得注意的是,这些CpGs表现出积极的调节作用，并位于肝脏和消化道中高表达的基因中，提示从基因组到通过DNA甲基化的能量代谢和吸收表型的潜在调节途径。横截面和纵向EWAS比较表明CpG与BMI和BMI变化相关的不同机制。
结论：这项研究增强了我们对BMI变化的表观遗传动力学的理解，并强调了纵向分析在破译表观遗传学与肥胖之间复杂的相互作用方面的价值。
