Huang J, Jiang Y
Department of Statistics and Actuarial Science, University of Iowa, Iowa City, Iowa 52242, USA.
Hum Hered. 2001;52(2):83-98. doi: 10.1159/000053359.
We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers.
我们研究了一种用于检验连锁关系的改良对数优势比分法（LD-lod）的性质，该方法纳入了连锁不平衡（LD-lod）。通过对其得分统计量的考察，我们表明LD-lod得分法自适应地结合了两种信息来源：（a）无论LD是否存在，对连锁关系都有信息价值的同源等位基因共享得分；（b）仅在存在LD时对连锁关系有信息价值的等位基因特异性同源等位基因共享得分之间的对比。我们还考虑了LD-lod得分法与三联体数据的传递不平衡检验（TDT）以及受累同胞对（ASP）数据的均值检验之间的联系。我们表明，对于三联体数据，隐性LD-lod检验在渐近意义上等同于TDT；对于ASP数据，它是TDT和ASP均值检验的自适应组合。我们证明，与本报告中考虑的广泛的LD范围和遗传模型相比，LD-lod得分法与ASP均值检验和TDT相比具有相对较好的统计效率。因此，当LD程度未知时，例如在使用密集遗传标记集进行全基因组筛选时，LD-lod得分法是一种用于检测连锁关系的有趣方法。
