Detecting disease associations due to linkage disequilibrium using haplotype tags: A class of tests and the determinants of statistical power
Detecting disease associations due to linkage disequilibrium using haplotype tags: A class of tests and the determinants of statistical power
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DOI：
10.1159/000073729
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发表时间：
2003-01-01
期刊：
影响因子：
1.8
通讯作者：
Clayton, DG
中科院分区：
文献类型：
--
作者：
Chapman, JM;Cooper, JD;Clayton, DG
在检测性状与DNA变异之间遗传关联的“间接”方法中，我们对连锁不平衡的基因或染色体区域中的若干标记进行分型。如果标记与性状之间存在关联，我们就假定该区域存在一种或多种致病性多态性。为了获得足够密集的标记集，几乎总是有必要使用单核苷酸多态性（SNP）。尽管关于选择一组最优的“单倍型标签SNP”（htSNP）以检测遗传区域与性状之间关联的方法已有一些文献报道，但对于此类研究完成后应如何分析，以及用于选择htSNP的原始数据应如何纳入分析这一问题，关注较少。本文针对基于群体和基于家系的关联研究讨论了这一问题。强调了因果位点与标记单倍型的各种评分方法之间关联的R - 2度量的作用。在大多数情况下，通常表明最简单的评分方法（位点编码），即不需要确定单倍型的相位，比包含单倍型信息的评分方法更有效力。还提出了一种新的“多位点传递不平衡检验（TDT）”。版权所有 (C) 2003 S. Karger AG，巴塞尔。
In the 'indirect' method of detecting genetic associations between a trait and a DNA variant, we type several markers in a gene or chromosome region of linkage disequilibrium. If there is association between markers and the trait, we presume the existence of one or more causal polymorphisms in the region. In order to obtain a sufficiently dense set of markers it will almost always be necessary to use single nucleotide polymorphisms (SNPs). Although there is an emerging literature on methods for choosing an optimal set of 'haplotype tag SNPs' (htSNPs) to detect association between a genetic region and a trait, less attention has been given to the problem of how such studies should be analysed when completed, and how the initial data which was used to select the htSNPs should be incorporated into the analysis. This paper discusses this problem for both population and family-based association studies. The role of the R-2 measure of association between a causal locus and various methods of scoring of marker haplotypes is highlighted. In most cases, the simplest method of scoring (locus coding), which does not require phase resolution, is shown generally to be more powerful than scoring methods that include haplotype information. A new 'multi-locus TDT' is also proposed. Copyright (C) 2003 S. Karger AG, Basel.