DNA methylation and body-mass index: a genome-wide analysis
DNA methylation and body-mass index: a genome-wide analysis
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DOI：
10.1016/s0140-6736(13)62674-4
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发表时间：
2014-06-07
期刊：
影响因子：
168.9
通讯作者：
Samani, Nilesh J.
中科院分区：
文献类型：
--
作者：
Dick, Katherine J.;Nelson, Christopher P.;Samani, Nilesh J.
肥胖是一个主要的健康问题，是由生活方式和环境及遗传因素之间的相互作用决定的。虽然已经确定了几种遗传变异与体重指数（BMI）之间的关联，但对与BMI相关的表观遗传变化知之甚少。我们进行了一个全基因组的甲基化分析在CpG位点的BMI。方法479个欧洲血统的人招募的心脏基因学联盟形成了我们的发现队列。我们使用Infinium HumanMethylation 450阵列对他们的全血DNA进行了分型。在质量控制后，检测甲基化水平与BMI的相关性。在来自MARTHA队列的339例北方欧洲血统的无关白色患者队列中，将假发现率q值为0.05或更低时显示与BMI相关的甲基化位点进行重复。在来自KORA队列的1789例欧洲血统的白色患者的第二个复制队列中检测了在该主要复制队列中保持显著性的位点。我们检查了在确定的位点的甲基化水平是否也显示出与来自参与MuTHER研究的白色女性个体的脂肪组织（n=635）和皮肤（n=395）的DNA中的BMI的关联。最后，我们研究了BMI相关位点的甲基化与遗传变异和基因表达的相关性。结果发现队列中的20个人在质量控制检查后被排除在分析之外，剩下459名参与者。在对协变量进行调整后，我们确定了一种关联（q值
Background Obesity is a major health problem that is determined by interactions between lifestyle and environmental and genetic factors. Although associations between several genetic variants and body-mass index (BMI) have been identified, little is known about epigenetic changes related to BMI. We undertook a genome-wide analysis of methylation at CpG sites in relation to BMI.Methods 479 individuals of European origin recruited by the Cardiogenics Consortium formed our discovery cohort. We typed their whole-blood DNA with the Infinium HumanMethylation450 array. After quality control, methylation levels were tested for association with BMI. Methylation sites showing an association with BMI at a false discovery rate q value of 0.05 or less were taken forward for replication in a cohort of 339 unrelated white patients of northern European origin from the MARTHA cohort. Sites that remained significant in this primary replication cohort were tested in a second replication cohort of 1789 white patients of European origin from the KORA cohort. We examined whether methylation levels at identified sites also showed an association with BMI in DNA from adipose tissue (n=635) and skin (n=395) obtained from white female individuals participating in the MuTHER study. Finally, we examined the association of methylation at BMI-associated sites with genetic variants and with gene expression.Findings 20 individuals from the discovery cohort were excluded from analyses after quality-control checks, leaving 459 participants. After adjustment for covariates, we identified an association (q value