Prioritization of genetic variants in the microRNA regulome as functional candidates in genome-wide association studies.
Prioritization of genetic variants in the microRNA regulome as functional candidates in genome-wide association studies.
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DOI：
10.1002/humu.22337
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发表时间：
2013-08
期刊：
影响因子：
3.9
通讯作者：
Sethupathy, Praveen
中科院分区：
文献类型：
--
作者：
Bulik-Sullivan, Brendan;Selitsky, Sara;Sethupathy, Praveen
对全基因组关联研究（GWAS）结果的综合分析表明，复杂的疾病/性状相关基因座富集于基因组的基因调控区域。对因果调控变异的研究主要集中在转录元件上，如启动子和增强子。microRNAs （miRNAs）现在被广泛认为是基因表达的关键转录后调节因子，并被认为赋予生物系统的稳定性。miRNA规则组中自然发生的遗传变异可能是人类表型变异的重要因素。然而，多态mirna介导的基因调控在多大程度上是GWAS信号的基础仍不清楚。在这项研究中，我们开发了迄今为止最全面的生物信息学分析管道，用于编目和优先排序miRNA规则组中的变体作为GWAS的功能候选物。我们强调了具体的发现，包括miRNA let-7启动子的变异，这可能有助于人类身高的变化。我们还讨论了如何在未来扩展我们的方法。总的来说，我们相信这项研究的结果将对有兴趣确定GWAS信号是否与miRNA规则组在其感兴趣的疾病/特征中相关的研究人员有价值。
Comprehensive analyses of results from genome-wide association studies (GWAS) have demonstrated that complex disease/trait-associated loci are enriched in gene regulatory regions of the genome. The search for causal regulatory variation has focused primarily on transcriptional elements, such as promoters and enhancers. microRNAs (miRNAs) are now widely appreciated as critical posttranscriptional regulators of gene expression and are thought to impart stability to biological systems. Naturally occurring genetic variation in the miRNA regulome is likely an important contributor to phenotypic variation in the human population. However, the extent to which polymorphic miRNA-mediated gene regulation underlies GWAS signals remains unclear. In this study, we have developed the most comprehensive bioinformatic analysis pipeline to date for cataloging and prioritizing variants in the miRNA regulome as functional candidates in GWAS. We highlight specific findings, including a variant in the promoter of the miRNA let-7 that may contribute to human height variation. We also provide a discussion of how our approach can be expanded in the future. Overall, we believe that the results of this study will be valuable for researchers interested in determining whether GWAS signals implicate the miRNA regulome in their disease/trait of interest.
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影响因子：
3.7
作者：
Corcoran DL;Pandit KV;Gordon B;Bhattacharjee A;Kaminski N;Benos PV
通讯作者：
Benos PV
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
DOI：
10.4161/cc.9.8.11202
发表时间：
2010-04-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Forman JJ;Coller HA
通讯作者：
Coller HA
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M