Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.
Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.
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DOI：
10.1080/15592294.2015.1080411
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lillycrop KA
中科院分区：
文献类型：
--
作者：
Huang RC;Garratt ES;Pan H;Wu Y;Davis EA;Barton SJ;Burdge GC;Godfrey KM;Holbrook JD;Lillycrop KA
儿童肥胖是一个重大的公共卫生问题。在这里，我们研究了差异 DNA 甲基化是否与儿童肥胖有关。我们研究了 78 名肥胖儿童（平均 BMI Z 得分：2.6）和 71 名年龄和性别匹配的对照（平均 BMI Z 得分：0.1）全血中的 DNA 甲基化谱。使用 Infinium HumanMmethylation450 BeadChip 阵列汇集并分析来自肥胖组和对照组的 DNA 样本。肥胖受试者和对照受试者之间的甲基化谱比较显示，有 129 个差异甲基化 CpG (DMCpG) 位点与 80 个独特基因相关，这些基因的甲基化差异大于 10%（P 值 < 0.05）。 DMCpG 中最丰富的途径包括发育过程、免疫系统调节、细胞信号传导调节和小 GTP 酶介导的信号转导。使用亚硫酸氢钠焦磷酸测序在个体受试者的 FYN、PIWIL4 和 TAOK3 基因内的基因座上验证所选 DMCpG 的甲基化与儿童肥胖之间的关联。 FYN 内的三个 CpG 位点在肥胖个体中高度甲基化（均 P < 0.01），而肥胖与 PIWIL4 (P = 0.003) 和 TAOK3 (P = 0.001) 内 CpG 位点的较低甲基化相关。建立逻辑回归模型后，我们确定，TAOK3 甲基化增加 1%，肥胖几率乘性降低 0.91（95% CI：0.86 – 0.97），FYN CpG3 甲基化增加 1%，肥胖几率乘性增加 1.03（95% CI：0.99 – 1.07）。总之，这些发现提供了证据表明儿童肥胖与全血中特定的 DNA 甲基化变化有关，这可能可用作肥胖风险的生物标志物。
Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 – 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 – 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.