Incorporating functional annotation information in prioritizing disease associated SNPs from genome wide association studies.
Incorporating functional annotation information in prioritizing disease associated SNPs from genome wide association studies.
复制标题
将功能注释信息纳入全基因组关联研究中疾病相关 SNP 的优先顺序。
DOI：
10.1007/s11427-014-4754-7
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Zhao,HongYu
中科院分区：
文献类型：
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作者：
Hou,Lin;Ma,TianZhou;Zhao,HongYu
随着基因分型和测序技术的最新进展，许多疾病易感性位点已被确定。然而，大部分的遗传性仍然无法解释，独立研究之间的重复率仍然很低。与此同时，在整个人类基因组的功能注释方面的努力也越来越多，例如DNA元件百科全书（ENCODE）项目和其他类似的项目。已经表明，结合这些功能注释来优先考虑全基因组关联信号可能有助于识别真正的关联信号。然而，据我们所知，当功能注释数据被认为是改善的程度还没有在文献中研究。在这篇文章中，我们提出了一个统计框架来估计注释数据的复制率的改善，并将其应用于克罗恩病和DNA酶I超敏位点。结果显示，使用细胞系特异性功能注释，预期的复制率得到改善，但仅在适度水平。
With recent advances in genotyping and sequencing technologies, many disease susceptibility loci have been identified. However, much of the genetic heritability remains unexplained and the replication rate between independent studies is still low. Meanwhile, there have been increasing efforts on functional annotations of the entire human genome, such as the Encyclopedia of DNA Elements (ENCODE) project and other similar projects. It has been shown that incorporating these functional annotations to prioritize genome wide association signals may help identify true association signals. However, to our knowledge, the extent of the improvement when functional annotation data are considered has not been studied in the literature. In this article, we propose a statistical framework to estimate the improvement in replication rate with annotation data, and apply it to Crohn’s disease and DNase I hypersensitive sites. The results show that with cell line specific functional annotations, the expected replication rate is improved, but only at modest level.