Phenotypically Enriched Genotypic Imputation in Genetic Association Tests.
Phenotypically Enriched Genotypic Imputation in Genetic Association Tests.
复制标题
遗传关联测试中表型丰富的基因型插补。
DOI：
10.1159/000446986
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发表时间：
2016
期刊：
影响因子：
1.8
通讯作者：
Lunetta,KathrynL
中科院分区：
文献类型：
--
作者：
Zhuang,WeiVivian;Murabito,JoanneM;Lunetta,KathrynL
背景：在纵向流行病学研究中，可能有具有丰富表型数据的个体在提供DNA用于遗传研究之前死亡或失访。通常，亲属的基因型和表型数据是可用的。分析不完整数据的两种策略是从分析中排除未分型的受试者（完整病例法，CC），并通过使用亲属的基因型进行基因型插补（GI）将表型但未分型的个体纳入分析。在这两种策略中，表型数据中的信息没有被用来处理缺失的genotype problem.Methods：我们提出了一种表型富集的基因型插补（PEGI）方法，使用EM（期望最大化）为基础的最大似然方法，将观察到的表型到genotype imputation.Results：我们的模拟与基因型完全随机缺失表明，对于一个单核苷酸多态性（SNP）与中度到强烈的影响表型，PEGI提高功率超过GI没有多余的I型错误。使用心脏研究的数据集，我们比较的PEGI，GI，和CC检测5个SNPs和年龄之间的关联在自然menopause.Conclusion：PEGI方法可以提高功率检测关联CC和GI在许多情况下。
Background:In longitudinal epidemiological studies there may be individuals with rich phenotype data who die or are lost to follow-up before providing DNA for genetic studies. Often, the genotypic and phenotypic data of the relatives are available. Two strategies for analyzing the incomplete data are to exclude ungenotyped subjects from analysis (the complete-case method, CC) and to include phenotyped but ungenotyped individuals in analysis by using relatives' genotypes for genotype imputation (GI). In both strategies, the information in the phenotypic data was not used to handle the missing-genotype problem.Methods:We propose a phenotypically enriched genotypic imputation (PEGI) method that uses the EM (expectation-maximization)-based maximum likelihood method to incorporate observed phenotypes into genotype imputation.Results:Our simulations with genotypes missing completely at random show that, for a single-nucleotide polymorphism (SNP) with moderate to strong effect on a phenotype, PEGI improves power more than GI without excess type I errors. Using the Framingham Heart Study data set, we compare the ability of the PEGI, GI, and CC to detect the associations between 5 SNPs and age at natural menopause.Conclusion:The PEGI method may improve power to detect an association over both CC and GI under many circumstances.