通过合并法和核方法检测家系结构样本中有序性状与基因变异之间的关联。

Testing for association between ordinal traits and genetic variants in pedigree-structured samples by collapsing and kernel methods.

作者信息

Chien Li-Chu

机构信息

Center for Fundamental Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

出版信息

Int J Biostat. 2023 Sep 26;20(2):677-690. doi: 10.1515/ijb-2022-0123. eCollection 2024 Nov 1.

Abstract

In genome-wide association studies (GWAS), logistic regression is one of the most popular analytics methods for binary traits. Multinomial regression is an extension of binary logistic regression that allows for multiple categories. However, many GWAS methods have been limited application to binary traits. These methods have improperly often been used to account for ordinal traits, which causes inappropriate type I error rates and poor statistical power. Owing to the lack of analysis methods, GWAS of ordinal traits has been known to be problematic and gaining attention. In this paper, we develop a general framework for identifying ordinal traits associated with genetic variants in pedigree-structured samples by collapsing and kernel methods. We use the local odds ratios GEE technology to account for complicated correlation structures between family members and ordered categorical traits. We use the retrospective idea to treat the genetic markers as random variables for calculating genetic correlations among markers. The proposed genetic association method can accommodate ordinal traits and allow for the covariate adjustment. We conduct simulation studies to compare the proposed tests with the existing models for analyzing the ordered categorical data under various configurations. We illustrate application of the proposed tests by simultaneously analyzing a family study and a cross-sectional study from the Genetic Analysis Workshop 19 (GAW19) data.

摘要

在全基因组关联研究(GWAS)中,逻辑回归是针对二元性状最常用的分析方法之一。多项回归是二元逻辑回归的扩展,可用于多类别情况。然而,许多GWAS方法在二元性状上的应用有限。这些方法常常被不适当地用于处理有序性状,这会导致不适当的I型错误率和较低的统计功效。由于缺乏分析方法,有序性状的GWAS一直存在问题并受到关注。在本文中,我们通过合并和核方法开发了一个通用框架,用于在谱系结构样本中识别与遗传变异相关的有序性状。我们使用局部优势比广义估计方程(GEE)技术来处理家庭成员之间复杂的相关结构以及有序分类性状。我们采用回顾性思路将遗传标记视为随机变量,以计算标记之间的遗传相关性。所提出的遗传关联方法能够处理有序性状并允许进行协变量调整。我们进行模拟研究,将所提出的检验与现有模型在各种配置下分析有序分类数据的情况进行比较。我们通过同时分析遗传分析研讨会19(GAW19)数据中的一个家系研究和一个横断面研究来说明所提出检验的应用。

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