Rational inferences about departures from Hardy-Weinberg equilibrium
Rational inferences about departures from Hardy-Weinberg equilibrium
复制标题
DOI：
10.1086/430507
复制
发表时间：
2005-06-01
影响因子：
9.8
通讯作者：
Cox, NJ
中科院分区：
文献类型：
--
作者：
Wittke-Thompson, JK;Pluzhnikov, A;Cox, NJ
以前的研究已经探索了使用偏离Hardy-Weinberg平衡（DHW）来精细映射孟德尔障碍和一般精细映射。其他研究使用Hardy-Weinberg测试进行基因分型质量控制。为了使研究者能够理性判断DHW是由于基因分型错误还是潜在的生物学，我们开发了一个分析框架和软件来确定DHW在常见疾病中可能出现的参数值。我们通过分析表明，对于一般疾病模型，易感位点人群和hardy - weinberg预期基因型频率（Delta）之间的差异是易感等位基因频率(q)、杂合子相对风险（beta）和纯合子相对风险（gamma）的函数。对于未受影响的对照样本，δ是非易感纯合子风险（α）、疾病人群患病率（K-p）、q、β和γ的函数。我们使用这些分析函数来计算D以及与常见疾病一致的一系列遗传模型（1.1）检测DHW所需的病例数或对照数
Previous studies have explored the use of departure from Hardy-Weinberg equilibrium (DHW) for fine mapping Mendelian disorders and for general fine mapping. Other studies have used Hardy-Weinberg tests for genotyping quality control. To enable investigators to make rational decisions about whether DHW is due to genotyping error or to underlying biology, we developed an analytic framework and software to determine the parameter values for which DHW might be expected for common diseases. We show analytically that, for a general disease model, the difference between population and Hardy-Weinberg-expected genotypic frequencies (Delta) at the susceptibility locus is a function of the susceptibility-allele frequency (q), heterozygote relative risk (beta), and homozygote relative risk (gamma). For unaffected control samples, Delta is a function of risk in nonsusceptible homozygotes (alpha), the population prevalence of disease (K-p), q, beta, and gamma. We used these analytic functions to calculate D and the number of cases or controls needed to detect DHW for a range of genetic models consistent with common diseases (1.1