Using linkage analysis of large pedigrees to guide association analyses.
Using linkage analysis of large pedigrees to guide association analyses.
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DOI：
10.1186/1753-6561-5-s9-s79
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发表时间：
2011-11-29
期刊：
影响因子：
--
通讯作者：
Jun G
中科院分区：
文献类型：
--
作者：
Choi SH;Liu C;Dupuis J;Logue MW;Jun G
迄今为止，全基因组关联研究已经发现了常见变异，部分解释了疾病和性状的家族聚集。由于测序成本大幅下降，研究人员现在将注意力转向不太常见的变异。然而，由于对大样本中的整个基因组进行测序成本高昂，因此必须非常小心地确定选择哪些样本和哪些基因组区域进行测序的优先顺序。我们有兴趣使用作为早期连锁研究的一部分收集的大型多重家族来识别用于深度测序的基因组区域。我们将连锁分析纳入 Q1 相关等位基因的搜索中。总的来说，我们发现全外显子组和连锁引导测序分析的功效都很低。通过将测序限制在具有高 LOD 峰的区域，我们发现比使用全外显子组测序更少的相关单核苷酸多态性。然而，结合连锁分析使我们能够检测到一半以上的相关易感性位点 (52%)，而这些位点本可以通过全外显子组测序来识别，而仅检查 2.5% 的外显子组。这一结果表明，整合来自大型多重家族的连锁结果可能会大大提高测序检测复杂疾病中性状相关等位基因的效率。
To date, genome-wide association studies have yielded discoveries of common variants that partly explain familial aggregation of diseases and traits. Researchers are now turning their attention to less common variants because the price of sequencing has dropped drastically. However, because sequencing of the whole genome in large samples is costly, great care must be taken to prioritize which samples and which genomic regions are selected for sequencing. We are interested in identifying genomic regions for deep sequencing using large multiplex families collected as part of earlier linkage studies. We incorporate linkage analysis into our search for Q1-associated alleles. Overall, we found that power was low for both whole-exome and linkage-guided sequencing analysis. By restricting sequencing to regions with high LOD peaks, we found fewer associated single-nucleotide polymorphisms than by using whole-exome sequencing. However, incorporating linkage analysis enabled us to detect more than half of the associated susceptibility loci (52%) that would have been identified by whole-exome sequencing while examining only 2.5% of the exome. This result suggests that incorporating linkage results from large multiplex families might greatly increase the efficiency of sequencing to detect trait-associated alleles in complex disease.