Lewinger Juan Pablo, Bull Shelley B
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Genet Epidemiol. 2006 Jan;30(1):62-76. doi: 10.1002/gepi.20125.
We propose a new test of linkage in the presence of allelic association that uses all available information in a sample of nuclear families, including parental phenotypes, genotypes from both affected and unaffected siblings, and families with homozygous parents. The test is based on the conditional framework developed by Rabinowitz and Laird [2000: Hum Hered 50:211-223] and is thus immune to population stratification and can be applied to families with any pattern of missing information. The test statistic is a conditional likelihood ratio based on a standard two-point linkage model with allelic association, where parameters are estimated from the sample. Through a simulation study, we determined that the proposed test has near optimal power for a wide range of scenarios, outperforming FBAT both when data were complete and when parental genotypes were missing, although differences between the two tests diminish as the genetic effect is reduced. To assess robustness, we also evaluated the performance of the tests under scenarios with population stratification and found that although there is a loss of efficiency, our proposed test remains a strong competitor to FBAT.
我们提出了一种在存在等位基因关联的情况下进行连锁分析的新检验方法，该方法利用核心家系样本中的所有可用信息，包括父母的表型、患病和未患病兄弟姐妹的基因型以及父母为纯合子的家系。该检验基于Rabinowitz和Laird [2000: Hum Hered 50:211 - 223] 开发的条件框架，因此不受群体分层的影响，并且可以应用于任何信息缺失模式的家系。检验统计量是基于具有等位基因关联的标准两点连锁模型的条件似然比，其中参数从样本中估计。通过模拟研究，我们确定所提出的检验在广泛的场景中具有接近最优的功效，在数据完整和父母基因型缺失的情况下均优于FBAT，尽管随着遗传效应的降低，两种检验之间的差异会减小。为了评估稳健性，我们还在存在群体分层的场景下评估了检验的性能，发现尽管效率有所损失，但我们提出的检验仍然是FBAT的有力竞争对手。
