DNA methylation and adiposity phenotypes: an epigenome-wide association study among adults in the Strong Heart Study.
DNA methylation and adiposity phenotypes: an epigenome-wide association study among adults in the Strong Heart Study.
复制标题
DOI：
10.1038/s41366-020-0646-z
复制
发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Navas-Acien A
中科院分区：
文献类型：
--
作者：
Crocker KC;Domingo-Relloso A;Haack K;Fretts AM;Tang WY;Herreros M;Tellez-Plaza M;Daniele Fallin M;Cole SA;Navas-Acien A
医学和公共卫生研究人员通常认为肥胖症是与心血管疾病、糖尿病和其他疾病相关的危险因素。现在认为这些健康挑战反映在 DNA 分子的表观遗传修饰上，例如 DNA 甲基化，它可以改变基因表达。在这里，我们报告了三项表观基因组广泛关联研究 (EWAS) 的结果，其中我们评估了强心脏研究中美国印第安成人参与者与三种肥胖表型（BMI、腰围和阻抗测量的身体脂肪百分比）相关的 DNA 差异甲基化（从外周血获得）。我们发现 8264 个 CpG 位点的差异甲基化至少与我们的三个响应变量之一相关。在我们测量的三个肥胖指标中，腰围的相关差异甲基化 CpG 数量最多，而体脂百分比的相关差异最低。由于腰围和身体脂肪百分比都与生理学相关，因此我们将解释重点放在这些变量上。我们在基因本体富集和差异甲基化区域分析中发现这两个变量之间的重叠程度较低，支持腰围和身体脂肪百分比测量代表生物学上不同的概念。我们对这些一般性发现的解释是，腰围分析中基因组（DMR）和合成途径（GO）的高度显着区域更有可能与内脏/腹部脂肪的存在相关，而不是更一般的肥胖指标。我们的研究结果证实了之前发现的许多与肥胖表型相关的差异甲基化 CpG 位点，同时我们还发现了以前未发现的新的差异甲基化 CpG 位点和区域。
Elevated adiposity is often posited by medical and public health researchers to be a risk factor associated with cardiovascular disease, diabetes, and other diseases. These health challenges are now thought to be reflected in epigenetic modifications to DNA molecules, such as DNA methylation, which can alter gene expression. Here we report the results of three Epigenome Wide Association Studies (EWAS) in which we assessed the differential methylation of DNA (obtained from peripheral blood) associated with three adiposity phenotypes (BMI, waist circumference, and impedance-measured percent body fat) among American Indian adult participants in the Strong Heart Study. We found differential methylation at 8264 CpG sites associated with at least one of our three response variables. Of the three adiposity proxies we measured, waist circumference had the highest number of associated differentially methylated CpGs, while percent body fat was associated with the lowest. Because both waist circumference and percent body fat relate to physiology, we focused interpretations on these variables. We found a low degree of overlap between these two variables in our gene ontology enrichment and Differentially Methylated Region analyses, supporting that waist circumference and percent body fat measurements represent biologically distinct concepts. We interpret these general findings to indicate that highly significant regions of the genome (DMR) and synthesis pathways (GO) in waist circumference analyses are more likely to be associated with the presence of visceral/ abdominal fat than more general measures of adiposity. Our findings confirmed numerous CpG sites previously found to be differentially methylated in association with adiposity phenotypes, while we also found new differentially methylated CpG sites and regions not previously identified.
登录
查看更多内容
影响因子：
2.2
作者：
Choromanska, B.;Mysliwiec, P.;Miklosz, A.
通讯作者：
Miklosz, A.
影响因子：
--
作者：
Buchta CM;Boi SK;Miller BJ;Milhem MM;Norian LA
通讯作者：
Norian LA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.2
作者：
Hunger, Jeffrey M.;Major, Brenda
通讯作者：
Major, Brenda
影响因子：
3.5
作者：
Demerath, Ellen W.;Guan, Weihua;Boerwinkle, Eric
通讯作者：
Boerwinkle, Eric