Liu Xin, Gordon Derek
Laboratory of Statistical Genetics, Rockefeller University, New York, New York 10021, USA.
Genet Epidemiol. 2003 Apr;24(3):208-19. doi: 10.1002/gepi.10232.
Based on the symmetry of transmitted/nontransmitted alleles from heterozygous parents under the null hypothesis of no association, the work proposed here establishes a general statistical framework for constructing association tests with data from nuclear families with multiple affected children. A class of association tests is proposed for both diallelic and multiallelic markers. The proposed test statistics reduce to the transmission disequilibrium test for trios, to T(su) by Martin et al. ([1997] Am. J. Hum. Genet. 61:439-448) for affected sib pairs, and to the pedigree disequilibrium test by Martin et al. ([2000] Am. J. Hum. Genet. 67:146-154); [2001] Am. J. Hum. Genet. 68:1065-1067) when using affected sibships only. The association test used in simulation and for real data (sitosterolemia) is the one which has the best overall power in detecting association. This association test is generally more powerful than the association tests proposed by Martin et al. ([2000] Am. J. Hum. Genet. 67:146-154); [2001] Am. J. Hum. Genet. 68:1065-1067) when using only affected sibships. For the sitosterolemia data set, the association test has its most significant result (P-value=0.0012) for the marker locus on the same bacterial artificial chromosome as the disease locus.
基于在无关联的零假设下杂合子父母传递/未传递等位基因的对称性，本文提出的工作建立了一个通用的统计框架，用于构建对有多个患病子女的核心家庭数据进行关联检验。针对双等位基因和多等位基因标记提出了一类关联检验。所提出的检验统计量在三人组中简化为传递不平衡检验，在患病同胞对中简化为Martin等人（[1997]《美国人类遗传学杂志》61:439 - 448）提出的T(su)，当仅使用患病同胞组时简化为Martin等人（[2000]《美国人类遗传学杂志》67:146 - 154；[2001]《美国人类遗传学杂志》68:1065 - 1067）提出的家系不平衡检验。在模拟和实际数据（谷甾醇血症）中使用的关联检验是在检测关联时总体效能最佳的检验。当仅使用患病同胞组时，这种关联检验通常比Martin等人（[2000]《美国人类遗传学杂志》67:146 - 154；[2001]《美国人类遗传学杂志》68:1065 - 1067）提出的关联检验效能更高。对于谷甾醇血症数据集，该关联检验在与疾病基因座位于同一细菌人工染色体上的标记基因座处得到了最显著的结果（P值 = 0.0012）。
