Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents
Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents
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DOI：
10.1038/s41598-019-38587-7
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发表时间：
2019-02-14
影响因子：
4.6
通讯作者：
Liao, Duanping
中科院分区：
文献类型：
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作者：
He, Fan;Berg, Arthur;Liao, Duanping
儿童肥胖在美国和世界范围内仍然是一种流行病。然而，关于青少年肥胖的表观遗传基础，人们知之甚少。为了研究肥胖相关基因的DNA甲基化水平与体重指数（BMI）百分位数之间的横断面关联，对263名青少年进行了基于人群的宾夕法尼亚州立大学儿童队列随访检查。利用外周白细胞提取的DNA，获得了胞嘧啶-磷酸-鸟嘌呤（CpG）位点及其周围区域DNA甲基化的全基因组单核苷酸分辨率。我们使用多变量调整线性回归模型来评估位点特异性甲基化水平与年龄和性别特异性BMI百分位数之间的关系。使用超几何和排列检验来确定肥胖相关基因是否在整个表观基因组中达到p < 0.05的所有基因内位点中显著富集。在5669个与BMI百分位数相关（p < 0.05）的位点中，有28个位于肥胖相关基因内。肥胖相关基因在103,466个基因内位点显著富集（P-hypergeometric = 0.006; P-permutation = 0.006）。此外，SIM1中一个位点甲基化的增加与较高的BMI百分位数显著相关（P = 4.02 -05）。如果外部验证，我们的数据将表明肥胖相关基因的DNA甲基化可能与青少年肥胖风险有关。
Childhood obesity remains an epidemic in the U.S. and worldwide. However, little is understood regarding the epigenetic basis of obesity in adolescents. To investigate the cross-sectional association between DNA methylation level in obesity-related genes and body mass index (BMI) percentile, data from 263 adolescents in the population-based Penn State Child Cohort follow-up exam was analysed. Using DNA extracted from peripheral leukocytes, epigenome-wide single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions was obtained. We used multivariable-adjusted linear regression models to assess the association between site-specific methylation level and age-and sex-specific BMI percentile. Hypergeometric and permutation tests were used to determine if obesity-related genes were significantly enriched among all intragenic sites that achieved a p < 0.05 throughout the epigenome. Among the 5,669 sites related to BMI percentile with p < 0.05, 28 were identified within obesity-related genes. Obesity-related genes were significantly enriched among 103,466 intragenic sites (P-hypergeometric = 0.006; P-permutation = 0.006). Moreover, increased methylation on one site within SIM1 was significantly related to higher BMI percentile (P = 4.2E-05). If externally validated, our data would suggest that DNA methylation in obesity-related genes may relate to obesity risk in adolescents.