Monte Carlo pedigree disequilibrium test for markers on the X chromosome
Monte Carlo pedigree disequilibrium test for markers on the X chromosome
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DOI：
10.1086/507609
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发表时间：
2006-09-01
影响因子：
9.8
通讯作者：
Liu, Yang
中科院分区：
文献类型：
--
作者：
Ding, Jie;Lin, Shili;Liu, Yang
由于疾病位点精细定位的需要和密集的单核苷酸多态性标记的可用性，许多形式的关联测试已经开发出来。其中大部分只适用于三合会，而有些则适用于核心家庭（兄弟姐妹）。虽然有一些方法可以处理大家庭（e。例如，在一个实施例中，系谱不平衡检验[PDT]），其中大多数不能容纳不完整的数据。此外，尽管有大量关于关联作图的文献，但只有非常有限数量的出版物适用于X染色体标记。在本报告中，我们首先将PDT扩展到X染色体上的标记，用于在存在连锁的情况下检测连锁不平衡。这种方法适用于任何谱系结构，称为“X染色体谱系不平衡检验”（XPDT）。然后，我们进一步扩展了XPDT，以适应某些个体（尤其是创始人）中缺失基因型的谱系。生成缺失基因型的蒙特卡罗（MC）样本并用于计算XMCPDT（X染色体MC PDT）统计量，其定义为给定不完整（观察）数据的XPDT统计量的条件期望。这个MC版本的XPDT仍然是一个有效的测试关联下的假设，即家系及其相关的情感模式是随机抽取的人口家系至少有一个受影响的后代。通过仿真将这组方法与现有方法进行比较，在所有考虑的设置中观察到大量的功率增益，I类错误率密切跟踪其标称值。
Because of the need for fine mapping of disease loci and the availability of dense single-nucleotide-polymorphismmarkers, many forms of association tests have been developed. Most of them are applicable only to triads, whereas some are amenable to nuclear families (sibships). Although there are a number of methods that can deal with extended families ( e. g., the pedigree disequilibrium test [PDT]), most of them cannot accommodate incomplete data. Furthermore, despite a large body of literature on association mapping, only a very limited number of publications are applicable to X-chromosomal markers. In this report, we first extend the PDT to markers on the X chromosome for testing linkage disequilibrium in the presence of linkage. This method is applicable to any pedigree structure and is termed "X-chromosomal pedigree disequilibrium test" (XPDT). We then further extend the XPDT to accommodate pedigrees with missing genotypes in some of the individuals, especially founders. Monte Carlo ( MC) samples of the missing genotypes are generated and used to calculate the XMCPDT (X-chromosomal MC PDT) statistic, which is defined as the conditional expectation of the XPDT statistic given the incomplete ( observed) data. This MC version of the XPDT remains a valid test for association under linkage with the assumption that the pedigrees and their associated affection patterns are drawn randomly from a population of pedigrees with at least one affected offspring. This set of methods was compared with existing approaches through simulation, and substantial power gains were observed in all settings considered, with type I error rates closely tracking their nominal values.