We present here four nonparametric statistics for linkage analysis that test whether pairs of affected relatives share marker alleles more often than expected. These statistics are based on simulating the null distribution of a given statistic conditional on the unaffecteds' marker genotypes. Each statistic uses a different measure of marker sharingthe SimAPM statistic uses the simulation-based affected-pedigree-member measure based on identity-by-state (IBS) sharing. The SimKIN (kinship) measure is 1.0 for identity-by-descent (IBD) sharing, 0.0 for no IBD status sharing, and the kinship coefficient when the IBD status is ambiguous. The simulation-based IBD (SimIBD) statistic uses a recursive algorithm to determine the probability of two affecteds sharing a specific allele IBD. The SimISO statistic is identical to SimIBD, except that it also measures marker similarity between unaffected pairs. We evaluated our statistics on data simulated under different two-locus disease models, comparing our results to those obtained with several other nonparametric statistics. Use of IBD information produces dramatic increases in power over the SimAPM method, which uses only IBS information. The power of our best statistic in most cases meets or exceeds the power of the other nonparametric statistics. Furthermore, our statistics perform comparisons between all affected relative pairs within general pedigrees and are not restricted to sib pairs or nuclear families.

译文

我们在这里提供了四个用于连锁分析的非参数统计数据,这些统计数据测试了受影响的亲戚对是否比预期的更频繁地共享标记等位基因。这些统计信息基于模拟给定统计信息的空分布,条件是未受影响的标记基因型。每个统计量使用不同的标记共享度量SimAPM统计量使用基于身份状态 (IBS) 共享的基于模拟的受影响谱系成员度量。SimKIN (亲属关系) 度量对于按血统身份 (IBD) 共享是1.0的,0.0对于没有IBD状态共享,并且当IBD状态不明确时是亲属系数。基于模拟的IBD (SimIBD) 统计量使用递归算法来确定两个情感共享特定等位基因IBD的概率。SimISO统计量与SimIBD相同,不同之处在于它还测量了未受影响的对之间的标记相似性。我们评估了在不同的两基因座疾病模型下模拟的数据的统计数据,并将我们的结果与其他几种非参数统计数据进行了比较。与仅使用IBS信息的SimAPM方法不同,使用IBD信息会大大提高功率。在大多数情况下,我们最好的统计量的能力达到或超过其他非参数统计量的能力。此外,我们的统计数据在一般谱系内所有受影响的相对对之间进行比较,并且不仅限于同胞对或核心家庭。

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