Testing for Hardy-Weinberg equilibrium at biallelic genetic markers on the X chromosome
Testing for Hardy-Weinberg equilibrium at biallelic genetic markers on the X chromosome
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DOI：
10.1038/hdy.2016.20
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发表时间：
2016-06-01
期刊：
影响因子：
3.8
通讯作者：
Weir, B. S.
中科院分区：
文献类型：
--
作者：
Graffelman, J.;Weir, B. S.
在大规模基因分型研究中，检测遗传标记的Hardy-Weinberg平衡（HWE）是检测基因分型错误的重要工具。对于X染色体上的标记，通常只对雌性进行chi（2）或精确检验，而半合子雄性被认为是没有信息的。在本文中，我们表明，男性是相关的，因为男性和女性之间的等位基因频率的差异可能表明HWE不举行。X染色体上标记的测试很少受到关注，在本文中，我们为测试HWE的双等位基因X染色体标记奠定了基础。我们开发了四个频率统计检验程序的X连锁标记，考虑男性和女性：卡方检验，似然比检验，精确检验和排列检验。包括男性的精确测试显示出更好的I型错误率。来自日内瓦静脉血栓栓塞项目的经验数据被用来说明拟议的测试。新的测试获得的结果与仅基于女性基因型计数的测试有很大不同。新的测试检测等位基因频率的差异，似乎能够发现额外的基因分型错误，这在仅基于女性的HWE测试中不会被注意到。
Testing genetic markers for Hardy-Weinberg equilibrium (HWE) is an important tool for detecting genotyping errors in large-scale genotyping studies. For markers at the X chromosome, typically the chi(2) or exact test is applied to the females only, and the hemizygous males are considered to be uninformative. In this paper we show that the males are relevant, because a difference in allele frequency between males and females may indicate HWE not to hold. The testing of markers on the X chromosome has received little attention, and in this paper we lay down the foundation for testing biallelic X-chromosomal markers for HWE. We develop four frequentist statistical test procedures for X-linked markers that take both males and females into account: the chi(2) test, likelihood ratio test, exact test and permutation test. Exact tests that include males are shown to have a better Type I error rate. Empirical data from the GENEVA project on venous thromboembolism is used to illustrate the proposed tests. Results obtained with the new tests differ substantially from tests that are based on female genotype counts only. The new tests detect differences in allele frequencies and seem able to uncover additional genotyping error that would have gone unnoticed in HWE tests based on females only.