Application of imputation methods to the analysis of rheumatoid arthritis data in genome-wide association studies.
Application of imputation methods to the analysis of rheumatoid arthritis data in genome-wide association studies.
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DOI：
10.1186/1753-6561-3-s7-s24
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发表时间：
2009-12-15
期刊：
影响因子：
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通讯作者：
Zhang K
中科院分区：
文献类型：
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作者：
Childers DK;Kang G;Liu N;Gao G;Zhang K
大多数遗传关联研究只对感兴趣区域中一小部分已编目的单核苷酸多态(SNPs)进行了基因分型。随着今天研究人员可以获得高密度SNP数据目录(例如，HapMap)，推测未分型SNPs的基因类型已成为可能。这反过来又允许我们测试那些未分类的SNPs，其动机是增加关联研究的力量。为此，已经开发了几种推算方法和相应的软件包。本研究的目的是将三种广泛使用的归因方法和相应的软件包应用于北美类风湿性关节炎协会在基因分析工作坊16中进行的类风湿性关节炎全基因组关联研究的数据，比较三种方法的性能，评估它们的优缺点，并确定类风湿性关节炎的其他易感基因。本文使用的软件包包括基于贝叶斯归因的关联作图程序(Bimbam)、病例对照关联研究中未观察到的基因型的推算程序(INPUTE)和用于检测未分型等位基因(金枪鱼)的程序。我们发现了一些与类风湿性关节炎显著相关的非类型性SNP。其中，有几个没有位于任何类型的SNP附近，这些SNP被发现是重要的，因此可能值得进一步研究。
Most genetic association studies only genotype a small proportion of cataloged single-nucleotide polymorphisms (SNPs) in regions of interest. With the catalogs of high-density SNP data available (e.g., HapMap) to researchers today, it has become possible to impute genotypes at untyped SNPs. This in turn allows us to test those untyped SNPs, the motivation being to increase power in association studies. Several imputation methods and corresponding software packages have been developed for this purpose. The objective of our study is to apply three widely used imputation methods and corresponding software packages to a data from a genome-wide association study of rheumatoid arthritis from the North American Rheumatoid Arthritis Consortium in Genetic Analysis Workshop 16, to compare the performances of the three methods, to evaluate their strengths and weaknesses, and to identify additional susceptibility loci underlying rheumatoid arthritis. The software packages used in this paper included a program for Bayesian imputation-based association mapping (BIMBAM), a program for imputing unobserved genotypes in case-control association studies (IMPUTE), and a program for testing untyped alleles (TUNA). We found some untyped SNP that showed significant association with rheumatoid arthritis. Among them, a few of these were not located near any typed SNP that was found to be significant and thus may be worth further investigation.