With rapid advancements of sequencing technologies and accumulations of electronic health records, a large number of genetic variants and multiple correlated human complex traits have become available in many genetic association studies. Thus, it becomes necessary and important to develop new methods that can jointly analyze the association between multiple genetic variants and multiple traits. Compared with methods that only use a single marker or trait, the joint analysis of multiple genetic variants and multiple traits is more powerful since such an analysis can fully incorporate the correlation structure of genetic variants and/or traits and their mutual dependence patterns. However, most of existing methods that simultaneously analyze multiple genetic variants and multiple traits are only applicable to unrelated samples. We develop a new method called MF‐TOWmuT to detect association of multiple phenotypes and multiple genetic variants in a genomic region with family samples. MF‐TOWmuT is based on an optimally weighted combination of variants. Our method can be applied to both rare and common variants and both qualitative and quantitative traits. Our simulation results show that (1) the type I error of MF‐TOWmuT is preserved; (2) MF‐TOWmuT outperforms two existing methods such as Multiple Family‐based Quasi‐Likelihood Score Test and Multivariate Family‐based Rare Variant Association Test in terms of power. We also illustrate the usefulness of MF‐TOWmuT by analyzing genotypic and phenotipic data from the Genetics of Kidneys in Diabetes study. R program is available at https://github.com/gaochengPRC/MF-TOWmuT.

中文翻译：

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MF-TOWmuT：使用家族数据测试具有多个特征的常见和稀有变异的最佳加权组合

随着测序技术的快速进步和电子健康记录的积累，大量遗传变异和多种相关的人类复杂性状已在许多遗传关联研究中可用。因此，开发能够联合分析多个遗传变异和多个性状之间关联的新方法变得必要且重要。与仅使用单一标记或性状的方法相比，多个遗传变异和多个性状的联合分析更强大，因为这种分析可以充分结合遗传变异和/或性状的相关结构及其相互依赖模式。然而，现有的大多数同时分析多个遗传变异和多个性状的方法仅适用于不相关的样本。我们开发了一种称为 MF-TOWmuT 的新方法来检测基因组区域中多种表型和多种遗传变异与家族样本的关联。MF-TOWmuT 基于变体的最佳加权组合。我们的方法可以应用于稀有和常见的变异以及定性和数量性状。我们的模拟结果表明（1）保留了MF-TOWmuT的I类误差；(2) MF-TOWmuT 在功效方面优于基于多家族的准似然评分检验和基于多元家族的稀有变体关联检验等两种现有方法。我们还通过分析糖尿病肾脏遗传学研究中的基因型和表型数据来说明 MF-TOWmuT 的有用性。R 程序可在 https://github.com/gaochengPRC/MF-TOWmuT 获得。