Detecting rare variant associations by identity-by-descent mapping in case-control studies.
Detecting rare variant associations by identity-by-descent mapping in case-control studies.
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DOI：
10.1534/genetics.111.136937
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发表时间：
2012-04
期刊：
影响因子：
3.3
通讯作者：
Thompson EA
中科院分区：
文献类型：
--
作者：
Browning SR;Thompson EA
血统同一性（IBD）映射测试病例是否比对照组在推定的因果变异周围共享更多IBD片段。IBD的这些片段可以从全基因组SNP数据中准确检测。我们研究IBD作图相对于SNP关联检测在全基因组病例对照SNP数据中的功效。我们特别关注罕见的变异，因为这些变异往往是最近的，因此更有可能有最近的共同祖先。我们模拟了来自大型和小型人群的数据，发现IBD作图和SNP关联测试的相对性能取决于人口统计学历史和对因果变异的选择强度。我们还提出了1型糖尿病数据集的IBD映射分析。在这些数据中，我们发现我们可以使用IBD映射检测仅与HLA区域的关联。总的来说，我们的研究结果表明，IBD映射可能有更高的权力比关联分析的SNP数据时，多个罕见的因果变异聚集在一个基因。然而，对于远交群体，可能需要非常大的样本量来获得全基因组显著性，除非因果变异具有强烈的影响。
Identity-by-descent (IBD) mapping tests whether cases share more segments of IBD around a putative causal variant than do controls. These segments of IBD can be accurately detected from genome-wide SNP data. We investigate the power of IBD mapping relative to that of SNP association testing for genome-wide case-control SNP data. Our focus is particularly on rare variants, as these tend to be more recent and hence more likely to have recent shared ancestry. We simulate data from both large and small populations and find that the relative performance of IBD mapping and SNP association testing depends on population demographic history and the strength of selection against causal variants. We also present an IBD mapping analysis of a type 1 diabetes data set. In those data we find that we can detect association only with the HLA region using IBD mapping. Overall, our results suggest that IBD mapping may have higher power than association analysis of SNP data when multiple rare causal variants are clustered within a gene. However, for outbred populations, very large sample sizes may be required for genome-wide significance unless the causal variants have strong effects.