Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci.
Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci.
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用于检测甲基化数量性状基因座的多性状多基因座关联的随机场建模。
DOI：
10.1093/bioinformatics/btac443
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Li,Ming
中科院分区：
文献类型：
--
作者：
Lyu,Chen;Huang,Manyan;Liu,Nianjun;Chen,Zhongxue;Lupo,PhilipJ;Tycko,Benjamin;Witte,JohnS;Hobbs,CharlotteA;Li,Ming
结果我们提出了一种多性状甲基化随机场(MULTI-MRF)方法来评价一组CpG位点和一组遗传变异之间的联合关联性。提出的方法有几个优点。首先，它是一种多性状方法，允许相邻CpG位点之间灵活的相关结构(例如，基于距离的相关)。第二，它也是一种综合了多种常见和稀有遗传变异效应的多基因座方法。第三，它用贝塔分布对甲基化特性进行建模，以表征它们的双峰和区间特性。通过仿真实验证明，在不同的疾病场景下，本文提出的方法比现有的一些方法具有更好的性能。我们通过对83个心脏组织样本的先天性心脏缺陷(CHD)研究的应用，进一步说明了所提出的方法。我们的结果表明，候选的甲基化数量性状基因BACE2与表达的QTL共定位于胫骨动脉中，并且在两个CHD全基因组关联研究中含有名义上显著相关的遗传变异。可获得性和implementationhttps://github.com/chenlyu2656/Multi-MRF.Supplementary信息补充数据可在生物信息学在线获得。
MotivationCpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another.ResultsWe propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models the methylation traits with a beta distribution to characterize their bimodal and interval properties. Through simulations, we demonstrated that the proposed method had improved power over some existing methods under various disease scenarios. We further illustrated the proposed method via an application to a study of congenital heart defects (CHDs) with 83 cardiac tissue samples. Our results suggested that geneBACE2, a methylation quantitative trait locus (QTL) candidate, colocalized with expression QTLs in artery tibial and harbored genetic variants with nominal significant associations in two genome-wide association studies of CHD.Availability and implementationhttps://github.com/chenlyu2656/Multi-MRF.Supplementary informationSupplementary data are available atBioinformaticsonline.
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