PDF(Pubmed)
Abstract：
Variability in quantitative traits has clinical, ecological, and evolutionary significance. Most genetic variants identified for complex quantitative traits have only a detectable effect on the mean of trait. We have developed the mean-variance test (MVtest) to simultaneously model the mean and log-variance of a quantitative trait as functions of genotypes and covariates by using estimating equations. The advantages of MVtest include the facts that it can detect effect modification, that multiple testing can follow conventional thresholds, that it is robust to non-normal outcomes, and that association statistics can be meta-analyzed. In simulations, we show control of type I error of MVtest over several alternatives. We identified 51 and 37 previously unreported associations for effects on blood-pressure variance and mean, respectively, in the UK Biobank. Transcriptome-wide association studies revealed 633 significant unique gene associations with blood-pressure mean variance. MVtest is broadly applicable to studies of complex quantitative traits and provides an important opportunity to detect novel loci.
摘要：
数量性状的变异性具有临床，生态,和进化意义。对于复杂的数量性状鉴定的大多数遗传变异仅对性状的平均值具有可检测的影响。我们已经开发了均值-方差检验（MVtest），通过使用估计方程将数量性状的均值和对数方差同时建模为基因型和协变量的函数。MVtest的优点包括它可以检测效果修改的事实，多重测试可以遵循传统的阈值，它对非正常结果是稳健的，关联统计可以进行荟萃分析。在模拟中,我们显示了对MVtest的I型误差对几种替代方案的控制。我们确定了51和37以前未报告的关联对血压方差和平均值的影响，分别,在英国生物银行。全转录组关联研究揭示了633个与血压均值方差显著的独特基因关联。MVtest广泛适用于复杂数量性状的研究，并为检测新基因座提供了重要的机会。
