Testing the association between single-nucleotide polymorphism (SNP) effects and a response is often carried out through kernel machine methods based on least squares, such as the sequence kernel association test (SKAT). However, these least-squares procedures are designed for a normally distributed conditional response, which may not apply. Other robust procedures such as the quantile regression kernel machine (QRKM) restrict the choice of the loss function and only allow inference on conditional quantiles. We propose a general and robust kernel association test with a flexible choice of the loss function, no distributional assumptions, and has SKAT and QRKM as special cases. We evaluate our proposed robust association test (RobKAT) across various data distributions through a simulation study. When errors are normally distributed, RobKAT controls type I error and shows comparable power with SKAT. In all other distributional settings investigated, our robust test has similar or greater power than SKAT. Finally, we apply our robust testing method to data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial to detect associations between selected genes including the major histocompatibility complex (MHC) region on chromosome six and neurotropic herpesvirus antibody levels in schizophrenia patients. RobKAT detected significant association with four SNP sets (HST1H2BJ, MHC, POM12L2, and SLC17A1), three of which were undetected by SKAT.

中文翻译：

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强大的内核关联测试（RobKAT）。

测试单核苷酸多态性（SNP）效果和响应之间的关联通常是通过基于最小二乘的核机器方法进行的，例如序列核关联测试（SKAT）。但是，这些最小二乘过程是为正态分布的条件响应而设计的，可能不适用。其他稳健的过程（如分位数回归内核机（QRKM））限制了损失函数的选择，仅允许对条件分位数进行推断。我们提出了一个通用且鲁棒的内核关联测试，可以灵活选择损失函数，没有分布假设，并且具有SKAT和QRKM作为特例。我们通过模拟研究评估了我们在各种数据分布中提出的鲁棒关联测试（RobKAT）。当错误被正常分配时，RobKAT控制I型错误，并显示出与SKAT相当的功能。在所有其他经调查的配电环境中，我们的稳健测试具有比SKAT相似或更高的功效。最后，我们将强大的测试方法应用于干预效果的临床抗精神病学试验（CATIE）临床试验中的数据，以检测精神分裂症患者中包括六号染色体上主要组织相容性复合体（MHC）区在内的选定基因与嗜神经性疱疹病毒抗体水平之间的关联。RobKAT检测到与四个SNP集（HST1H2BJ，MHC，POM12L2和SLC17A1）显着相关，其中三个未被SKAT检测到。我们将强大的测试方法应用于干预效果的临床抗精神病临床试验（CATIE）临床试验中的数据，以检测精神分裂症患者中包括六号染色体上主要组织相容性复合体（MHC）区域在内的选定基因与嗜神经性疱疹病毒抗体水平之间的关联。RobKAT检测到与四个SNP集（HST1H2BJ，MHC，POM12L2和SLC17A1）显着相关，其中三个未被SKAT检测到。我们将强大的测试方法应用于干预效果的临床抗精神病学试验（CATIE）临床试验中的数据，以检测精神分裂症患者中包括六号染色体上主要组织相容性复合体（MHC）区域在内的选定基因与嗜神经性疱疹病毒抗体水平之间的关联。RobKAT检测到与四个SNP集（HST1H2BJ，MHC，POM12L2和SLC17A1）显着相关，其中三个未被SKAT检测到。