Gene-Centric Characteristics of Genome-Wide Association Studies
Gene-Centric Characteristics of Genome-Wide Association Studies
复制标题
DOI：
10.1371/journal.pone.0001262
复制
发表时间：
2007-12-05
期刊：
影响因子：
3.7
通讯作者：
Li, Yixue
中科院分区：
文献类型：
--
作者：
Dong, Changzheng;Qian, Ziliang;Li, Yixue
背景高通量基因分型芯片为全基因组关联（GWA）研究发现新的疾病易感性单核苷酸多态性（SNPs）做出了巨大贡献。高密度芯片的设计使用两种不同的SNP选择方法，直接基因为中心的方法，和间接的准随机SNP或连锁不平衡（LD）为基础的tagSNP方法。尽管所有这些方法都可以提供高的基因组覆盖率并确定基因中的变异，但尚不清楚这些方法可以在多大程度上捕获常见的基因变异。同样重要的是要描述和比较这些方法之间的差异。方法/主要调查结果。在我们的研究中，通过使用II期HapMap数据和从OMIM中提取的疾病变体，首先进行以基因为中心的评估，以评估这些方法在高加索人群中捕获疾病变体的能力。在基因区域、进化保守内含子和非基因区域、本体和通路等方面对SNPs的分布模式进行了描述。结果表明，无论采用哪种SNP选择方法，目前的高密度SNP芯片在基因区域的覆盖率都很高，可以捕获HapMap框架下的大多数已知常见疾病变异。结果还表明，直接和间接的方法之间的差异相对较小。两者在这些基因中心特征中具有相似的SNP分布模式。结论/意义。这项研究表明，间接方法不仅具有高覆盖率的优势，而且对于专注于直接方法支持的基因或保守区域中的各种功能SNP的研究也是有用的。该研究和特征注释将有助于设计和分析GWA研究，旨在识别常见疾病的遗传风险因素，特别是基因和保守区域的变异。
Background. The high-throughput genotyping chips have contributed greatly to genome-wide association (GWA) studies to identify novel disease susceptibility single nucleotide polymorphisms ( SNPs). The high-density chips are designed using two different SNP selection approaches, the direct gene-centric approach, and the indirect quasi-random SNPs or linkage disequilibrium (LD)-based tagSNPs approaches. Although all these approaches can provide high genome coverage and ascertain variants in genes, it is not clear to which extent these approaches could capture the common genic variants. It is also important to characterize and compare the differences between these approaches. Methodology/Principal Findings. In our study, by using both the Phase II HapMap data and the disease variants extracted from OMIM, a gene-centric evaluation was first performed to evaluate the ability of the approaches in capturing the disease variants in Caucasian population. Then the distribution patterns of SNPs were also characterized in genic regions, evolutionarily conserved introns and nongenic regions, ontologies and pathways. The results show that, no mater which SNP selection approach is used, the current high-density SNP chips provide very high coverage in genic regions and can capture most of known common disease variants under HapMap frame. The results also show that the differences between the direct and the indirect approaches are relatively small. Both have similar SNP distribution patterns in these gene-centric characteristics. Conclusions/Significance. This study suggests that the indirect approaches not only have the advantage of high coverage but also are useful for studies focusing on various functional SNPs either in genes or in the conserved regions that the direct approach supports. The study and the annotation of characteristics will be helpful for designing and analyzing GWA studies that aim to identify genetic risk factors involved in common diseases, especially variants in genes and conserved regions.