Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 HP, Nijmegen, The Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700RB, Groningen, The Netherlands.
Brief Bioinform. 2022 Sep 20;23(5). doi: 10.1093/bib/bbac287.
Genetic association studies have been very successful at elucidating the genetic background of many complex diseases/traits. However, the X-chromosome is often neglected in these studies because of technical difficulties and the fact that most tools only utilize genetic data from autosomes. In this review, we aim to provide an overview of different practical approaches that are followed to incorporate the X-chromosome in association analysis, such as Genome-Wide Association Studies and Expression Quantitative Trait Loci Analysis. In general, the choice of which test statistics is most appropriate will depend on three main criteria: (1) the underlying X-inactivation model, (2) if Hardy-Weinberg equilibrium holds and sex-specific allele frequencies are expected and (3) whether adjustment for confounding variables is required. All in all, it is recommended that a combination of different association tests should be used for the analysis of X-chromosome.
遗传关联研究在阐明许多复杂疾病/特征的遗传背景方面非常成功。然而，由于技术困难以及大多数工具仅利用常染色体遗传数据的事实，X 染色体在这些研究中经常被忽视。在这篇综述中，我们旨在提供不同实用方法的概述，这些方法被用来将 X 染色体纳入关联分析中，例如全基因组关联研究和表达数量性状基因座分析。一般来说，选择最合适的检验统计量将取决于三个主要标准：（1）潜在的 X 染色体失活模型，（2）是否遵守 Hardy-Weinberg 平衡以及是否预期存在性别特异性等位基因频率，（3）是否需要调整混杂变量。总之，建议使用不同的关联测试的组合来分析 X 染色体。
