Effects of stratification in the analysis of affected-sib-pair data: Benefits and costs
Effects of stratification in the analysis of affected-sib-pair data: Benefits and costs
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DOI：
10.1086/302748
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发表时间：
2000-02-01
影响因子：
9.8
通讯作者：
Ott, J
中科院分区：
文献类型：
--
作者：
Leal, SM;Ott, J
在三种情况下检查了受影响同胞对 (ASP) 数据分层的收益和成本：(1) 当分层和非分层 ASP 数据集之间的血统身份 (IBD) 等位基因共享没有差异时； (2) 当某一分层组中 IBD 等位基因共享增加时； (3)当根据一个基因座上的IBD等位基因共享状态对数据进行分层时，然后分析分层的ASP在第二个基因座上的连锁。当各层之间的 IBD 共享没有差异时，总是会因分层数据而受到惩罚。分层 ASP 数据集中检测关联性的能力丧失是多次测试和各个层内样本量较小的结果。在病因异质性（即表型的严重程度、发病年龄）代表遗传异质性的情况下，可以通过对 ASP 数据进行分层来提高检测连锁的能力。当有足够的 IBD 等位基因共享和样本量时，就会获得这种好处。一旦给定基因座建立了连锁，就可以根据该基因座的 IBD 状态对数据进行分层，并可以测试第二个基因座的连锁。当相对风险接近 1 时，对于未分层的 ASP 数据集，检测第二个基因座处连锁的功效始终较大。即使相对风险值与 1 相差很大，并且样本量足够并且 IBD 等位基因共享，对 ASP 数据进行分层的好处也是微乎其微的。
The benefits and costs of stratification of affected-sib-pair (ASP) data were examined in three situations: (1) when there is no difference in identity-by-descent (IBD) allele sharing between stratified and unstratified ASP data sets; (2) when there is an increase in IBD allele sharing in one of the stratified groups; and (3) when the data are stratified on the basis of IBD allele-sharing status at one locus, and the stratified ASPs are then analyzed for linkage at a second locus. When there is no difference in IBD sharing between strata, a penalty is always paid for stratifying the data. The loss of power to detect linkage in the stratified ASP data sets is the result of multiple testing and the smaller sample size within individual strata. In the case in which etiologic heterogeneity (i.e., severity of phenotype, age at onset) represents genetic heterogeneity, the power to detect linkage can be increased by stratifying the ASP data. This benefit is obtained when there is sufficient IBD allele sharing and sample sizes. Once linkage has been established for a given locus, data can be stratified on the basis of IBD status at this locus and can be tested for linkage at a second locus. When the relative risk is in the vicinity of 1, the power to detect linkage at the second locus is always greater for the unstratified ASP data set. Even for values of the relative risk that diverge sufficiently from 1, with adequate sample sizes and IBD allele sharing, the benefits of stratifying ASP data are minimal.