Exact Inference for Hardy-Weinberg Proportions with Missing Genotypes: Single and Multiple Imputation.
Exact Inference for Hardy-Weinberg Proportions with Missing Genotypes: Single and Multiple Imputation.
复制标题
具有缺失基因型的Hardy-Weinberg比例的精确推断：单次和多个插补。
DOI：
10.1534/g3.115.022111
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发表时间：
2015-09-15
期刊：
影响因子：
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通讯作者：
Weir BS
中科院分区：
文献类型：
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作者：
Graffelman J;Nelson S;Gogarten SM;Weir BS
本文解决了在缺失基因型数据存在的情况下，基于精确检验的Hardy - Weinberg平衡统计推断问题。当对Hardy - Weinberg平衡进行标记测试时，缺失的基因型通常被丢弃，这可能导致有关平衡的统计推断存在偏差。单次和多次输入都可以提高对均衡的推断。我们通过使用近交系数（或等效的χ2统计量）和精确p值来开发缺失存在下的平衡检验。对日内瓦早产儿项目中缺失率高的一组标记物的分析表明，当考虑到缺失时，关于平衡的确切推断可以大大改变。对于缺失率高的标记（约5%），我们发现单次和多次代入都倾向于减少Hardy - Weinberg不平衡的证据。根据所使用的归算方法，6 - 13%的测试结果在5%的水平上发生定性变化。
This paper addresses the issue of exact-test based statistical inference for Hardy−Weinberg equilibrium in the presence of missing genotype data. Missing genotypes often are discarded when markers are tested for Hardy−Weinberg equilibrium, which can lead to bias in the statistical inference about equilibrium. Single and multiple imputation can improve inference on equilibrium. We develop tests for equilibrium in the presence of missingness by using both inbreeding coefficients (or, equivalently, χ2 statistics) and exact p-values. The analysis of a set of markers with a high missing rate from the GENEVA project on prematurity shows that exact inference on equilibrium can be altered considerably when missingness is taken into account. For markers with a high missing rate (>5%), we found that both single and multiple imputation tend to diminish evidence for Hardy−Weinberg disequilibrium. Depending on the imputation method used, 6−13% of the test results changed qualitatively at the 5% level.