Epigenetic Mediators Between Childhood Socioeconomic Disadvantage and Mid-Life Body Mass Index: The New England Family Study.
Epigenetic Mediators Between Childhood Socioeconomic Disadvantage and Mid-Life Body Mass Index: The New England Family Study.
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童年社会经济劣势与中年体重指数之间的表观遗传中介因素：新英格兰家庭研究。
DOI：
10.1097/psy.0000000000000411
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发表时间：
2016
影响因子：
3.3
通讯作者：
Kelsey,KarlT
中科院分区：
文献类型：
--
作者：
Loucks,EricB;Huang,Yen-Tsung;Agha,Golareh;Chu,Su;Eaton,CharlesB;Gilman,StephenE;Buka,StephenL;Kelsey,KarlT
目的儿童社会经济劣势与成年肥胖风险相关；然而，人们对表观遗传机制知之甚少。这项工作的目的是评估儿童社会经济劣势与成年体重指数 (BMI) 之间的关联是否是由 DNA 甲基化介导的。方法参与者是来自新英格兰家庭研究的 141 名男性和女性，对平均年龄 47 岁进行前瞻性产前随访。使用 Infinium HumanMmethylation450K BeadChip 对成年时获得的外周血和脂肪组织中的表观基因组 DNA 甲基化进行了评估。 7 岁时的儿童社会经济地位 (SES) 直接根据父母的报告进行评估。使用平均年龄 47 岁的 BMI 直接评估后代肥胖情况。使用最小二乘估计器估计 SES、DNA 甲基化和 BMI 之间的关联。使用联合显着性检验和 bootstrapping 进行统计中介分析。结果在表观基因组甲基化 BMI 分析中，CpG 位点在 25% 错误发现率水平上显着，男性中的 91 个位点和女性中的 71 个位点对于脂肪组织中的 SES 甲基化关联也具有显着性 (p<.001)。许多涉及与肥胖发展具有生物学相关性的基因，包括脂肪酸合酶、跨膜蛋白 88、信号转导器和转录激活剂 3 以及神经突蛋白 1。没有证据表明外周血白细胞中存在表观遗传介导。结论 特定基因的 DNA 甲基化可能是儿童社会经济劣势与中年之间关联的介导因素 脂肪组织中的 BMI。研究结果激励我们继续努力研究儿童社会经济劣势是否以及如何在生物学上嵌入与肥胖病因相关的区域的表观基因组水平。
ObjectiveChildhood socioeconomic disadvantage is associated with adulthood obesity risk; however, epigenetic mechanisms are poorly understood. This work's objective was to evaluate whether associations of childhood socioeconomic disadvantage with adulthood body mass index (BMI) are mediated by DNA methylation.MethodsParticipants were 141 men and women from the New England Family Study, prospectively followed prenatally through a mean age of 47 years. Epigenomewide DNA methylation was evaluated in peripheral blood and adipose tissue obtained at adulthood, using the Infinium HumanMethylation450K BeadChip. Childhood socioeconomic status (SES) at age 7 years was assessed directly from parents' reports. Offspring adiposity was directly assessed using BMI at a mean age of 47 years. Associations of SES, DNA methylation, and BMI were estimated using least square estimators. Statistical mediation analyses were performed using joint significance test and bootstrapping.ResultsOf CpG sites significant at the 25% false discovery rate level in epigenomewide methylation BMI analyses, 91 sites in men and 71 sites in women were additionally significant for SES-methylation associations (p<. 001) in adipose tissue. Many involved genes biologically relevant for development of obesity, including fatty acid synthase, transmembrane protein 88, signal transducer and activator of transcription 3, and neuritin 1. There was no evidence of epigenetic mediation in peripheral blood leukocytes.ConclusionsDNA methylation at specific genes may be mediators of associations between childhood socioeconomic disadvantage and mid-life BMI in adipose tissue. Findings motivate continued efforts to study if and how childhood socioeconomic disadvantage is biologically embedded at the level of the epigenome in regions etiologically relevant for adiposity.