Cleves M A, Dawson D V, Elston R C, Schnell A H
Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, Case Western Reserve University, Cleveland, Ohio 44109, USA.
Genet Epidemiol. 1997;14(6):581-6. doi: 10.1002/(SICI)1098-2272(1997)14:6<581::AID-GEPI5>3.0.CO;2-2.
We applied a new test statistic for linkage that removes the traditional assumption of equal female (theta f) and male (theta m) recombination fractions by testing Ho: theta f + theta m = 1 vs. HA: theta f + theta m < 1 to GAW10 Problem 1. Specifically we reanalyzed the reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al. [1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41. Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.
我们将一种新的连锁检验统计量应用于GAW10问题1，该统计量通过检验原假设Ho：θf + θm = 1与备择假设HA：θf + θm < 1，消除了女性（θf）和男性（θm）重组率相等这一传统假设。具体而言，我们重新分析了已报道的18号染色体上双相情感障碍的一个假定易感基因座与标记D18S41之间可能存在的连锁关系[Stine等人，1995年]。我们使用了符合Stine等人[1995年]所使用描述的外显率函数，假定为连续的年龄依赖性逻辑分布。在假定哈迪-温伯格平衡的情况下估计了最大似然标记等位基因频率。传统对数计分分析的结果并不强烈支持疾病基因座与标记D18S41之间存在连锁关系。同样，新的连锁检验统计量也未能提供支持连锁关系的证据。无论假定的是显性还是隐性遗传模型，也无论分析包括所有可用家系还是仅限于父系传递的家系，都是如此。我们的对数计分与Stine等人[1995年]所获得的对数计分之间发现的显著差异，可归因于在年龄依赖性外显率函数、标记等位基因频率或两者方面所做假设的差异。
