Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes
Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes
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DOI：
10.1007/s10038-008-0258-2
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Nakamura, Junichiro
中科院分区：
文献类型：
--
作者：
Kitamura, Nobutaka;Akazawa, Kouhei;Nakamura, Junichiro
两阶段关联研究是有效识别疾病易感基因最常用的方法。然而，最近的一些单核苷酸多态性（SNP）研究最近采用了三阶段设计。本研究的目的是调查多阶段设计中基于复制的分析 (RBA) 和联合分析 (JA) 的统计功效和阳性预测值 (PPV) 的实际特性。为此，开发了多阶段设计程序，以计算样本数量、候选等位基因、最后阶段剩余等位基因和基因分型等各种条件下的这些性能指标。结果表明，在第一阶段样本量比例小于0.5的范围内，三阶段设计中RBA和JA的功效和PPV均高于两阶段设计。这种趋势在JA中更为显着。总之，进行SNP研究以确定疾病易感基因的研究人员需要考虑三阶段病例对照关联研究，与样本总数、等位基因和基因分型等研究条件相对应。此外，本研究中开发的程序对于在规划多阶段关联研究中估计功效和 PPV 很有用。
A two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.