Levinson D F
Department of Psychiatry, Medical College of Pennsylvania, and Hahneman University, Philadelphia 19129, USA.
Genet Epidemiol. 1995;12(6):631-5. doi: 10.1002/gepi.1370120618.
A haplotype-based haplotype relative risk (HHRR) analysis of simulated data for 200 affected offspring and their parents (Genetic Analysis Workshop 9, Problem 1) detected linkage disequilibrium at 2 of 360 marker loci. An additive model was suggested but not proven by haplotypes of affected vs. unaffected offspring. These findings were consistent with the generating model. Affected sib pair analysis failed to detect additional loci. Discussion among workshop participants suggested that the chi-square test used here (2 [transmitted vs. nontransmitted] x n [alleles] for each locus) was invalid because of the nonindependence of proportions of transmitted alleles. In post-workshop analyses, transmission disequilibrium tests (TDTs) for each allele at each locus detected only the true associations if p values were corrected by one of two methods: Bonferroni correction for 2,035 TDTs, or correcting each test for n (number of tests at the locus) minus 1 and then for the number of loci tested. Screening loci for linkage disequilibrium requires careful attention to correction for multiple comparisons.
对200名患病后代及其父母的模拟数据（遗传分析研讨会9，问题1）进行基于单倍型的单倍型相对风险（HHRR）分析，在360个标记位点中的2个位点检测到连锁不平衡。提出了一个加性模型，但未通过患病与未患病后代的单倍型得到证实。这些发现与生成模型一致。患病同胞对分析未能检测到其他位点。研讨会参与者之间的讨论表明，这里使用的卡方检验（每个位点2[传递与未传递]×n[等位基因]）无效，因为传递等位基因比例不独立。在研讨会后的分析中，每个位点每个等位基因的传递不平衡检验（TDT）只有在通过以下两种方法之一校正p值时才能检测到真正的关联：对2035次TDT进行Bonferroni校正，或对每个检验先校正n（该位点的检验次数）减1，然后再校正所检验的位点数量。筛选连锁不平衡位点需要仔细注意多重比较的校正。
