Modeling methylation data as an additional genetic variance component.
Modeling methylation data as an additional genetic variance component.
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DOI：
10.1186/s12919-018-0128-7
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Blangero J
中科院分区：
文献类型：
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作者：
Almeida M;Peralta J;Garcia J;Diego V;Goring H;Williams-Blangero S;Blangero J
高通量平台允许对数千个先前已知的甲基化位点进行表征。这些平台在研究部分负责基因表达控制的表观遗传效应方面具有巨大的潜力。甲基化位点通过甲基化状态的改变为研究环境对基因组事件的实时贡献提供了一座桥梁。利用GAW20的S组委会提供的数据，计算了服用调脂药物非诺贝特前后各胞嘧啶-磷酸-鸟嘌呤(CPG)岛的遗传度。令人惊讶的是，在使用药物之前，我们检测到了相当高的遗传力估计。这种有点出乎意料的高样本相关性通过使用主成分和非诺贝特治疗前后遗传力估计的分布得到纠正，这使得分布具有可比性。收集了位于基因附近的甲基化位点，并估计了代表样本之间总体相关性的遗传关系矩阵。我们实施了一项随机效应关联测试，以筛选其甲基化模式部分解释可观察到的高密度脂蛋白(HDL)遗传性的基因。我们观察到的主要关联是TMEM52基因，它编码一种跨膜蛋白，主要在肝脏表达，在此之前从未与高密度脂蛋白相关。通过使用线性混合模型的方差分量分解框架，可以集成来自不同来源的数据，如甲基化、基因表达、代谢组学和蛋白质组学。遗传方差分量分解的分解为这个新的组学时代的挑战提供了一种灵活的分析方法。
High-throughput platforms allow the characterization of thousands of previously known methylation sites. These platforms have great potential for investigating the epigenetic effects that are partially responsible for gene expression control. Methylation sites provide a bridge for the investigation of real-time environmental contributions on genomic events by the alteration of methylation status of those sites. Using the data provided by GAW20’s organization committee, we calculated the heritability estimates of each cytosine-phosphate-guanine (CpG) island before and after the use of fenofibrate, a lipid-control drug. Surprisingly, we detected substantially high heritability estimates before drug usage. This somewhat unexpected high sample correlation was corrected by the use of principal components and the distributions of heritability estimates before and after fenofibrate treatment, which made the distributions comparable. The methylation sites located near a gene were collected and a genetic relationship matrix estimated to represent the overall correlation between samples. We implemented a random-effect association test to screen genes whose methylation patterns partially explain the observable high-density lipoprotein (HDL) heritability. Our leading association was observed for the TMEM52 gene that encodes a transmembrane protein, and is largely expressed in the liver, had not been previously associated with HDL until this manuscript. Using a variance component decomposition framework with the linear mixed model allows the integration of data from different sources, such as methylation, gene expression, metabolomics, and proteomics. The decomposition of the genetic variance component decomposition provides a flexible analytical approach for the challenges of this new omics era.