Yu Chang, Zhang Sanguo, Zhou Chuan, Sile Saba
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2158, USA.
Genet Epidemiol. 2009 Apr;33(3):275-80. doi: 10.1002/gepi.20381.
Testing Hardy-Weinberg equilibrium (HWE) in the control group is commonly used to detect genotyping errors in genetic association studies. We propose a likelihood ratio test for testing HWE in the study population using both case and control samples. This test incorporates underlying association models. Another feature is that, when we infer the disease-genotype association, we explicitly incorporate HWE or a possible departure from Hardy-Weinberg equilibrium (DHWE) into the model. Our unified framework enables us to infer the disease-genotype association when a detected DHWE needs to be part of the model after causes for the DHWE are explored. Real data sets are used to illustrate the application of the methodology and its implication in genetic association studies. Our analysis and interpretation touch on issues such as genotyping errors, population selection, population stratification, or the study sampling plan, that all could be the cause of DHWE.
在对照组中检验哈迪-温伯格平衡（HWE）常用于检测基因关联研究中的基因分型错误。我们提出了一种似然比检验，用于使用病例和对照样本在研究人群中检验HWE。该检验纳入了潜在的关联模型。另一个特点是，当我们推断疾病-基因型关联时，我们明确地将HWE或与哈迪-温伯格平衡的可能偏离（DHWE）纳入模型。我们的统一框架使我们能够在探索DHWE的原因后，在检测到的DHWE需要成为模型一部分时推断疾病-基因型关联。使用实际数据集来说明该方法的应用及其在基因关联研究中的意义。我们的分析和解释涉及基因分型错误、人群选择、人群分层或研究抽样计划等问题，所有这些都可能是DHWE的原因。
