BACKGROUND/AIMS Unlike the gene-poor Y chromosome, the X chromosome contains over 1,000 genes that are essential for viability of cells. Females have 2 X chromosomes, and thus female X-linked gene expression would be expected to be twice that of males. To adjust this imbalance, one of the 2 X-linked genes is often inactivated, and this is known as X-chromosome inactivation (XCI). However, recent studies described that a gene can be nonrandomly selected for inactivation from 2 X-linked genes and that XCI is not observed in some X-linked genes. Since this complex biological process has prevented efficient statistical association analyses, we propose a new statistical method against this uncertain biological process. METHODS The proposed method consists of 2 steps. First, p values for various biological processes are calculated and then combined into a single p value with the modified Fisher method and a minimum p value. RESULTS Our simulation results show that the proposed method is generally the most statistically efficient and is not sensitive to the unknown biological model. CONCLUSION Therefore, we can conclude that the proposed approaches are robust against the various XCI processes for testing the association of X-linked single nucleotide polymorphisms with the disease of interest and the proposed method is a practical solution.

中文翻译：

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X链接变体的关联分析的有效统计方法。

背景/目的与缺乏基因的Y染色体不同，X染色体包含1000多个基因，这些基因对于细胞的生存能力至关重要。雌性有2条X染色体，因此，雌性X连锁基因的表达预计将是雄性的两倍。为了调节这种不平衡，经常将2个X连锁基因之一失活，这被称为X染色体失活（XCI）。但是，最近的研究表明，可以从2个X连锁基因中非随机选择一个基因进行灭活，并且在某些X连锁基因中未观察到XCI。由于此复杂的生物过程阻止了有效的统计关联分析，因此我们针对这种不确定的生物过程提出了一种新的统计方法。方法所提出的方法包括2个步骤。第一的，计算出各种生物过程的p值，然后用改进的Fisher方法将其组合为单个p值和最小p值。结果我们的仿真结果表明，所提出的方法通常在统计上最有效，并且对未知的生物学模型不敏感。结论因此，我们可以得出结论，所提出的方法对于测试X连锁单核苷酸多态性与所关注疾病的关联的各种XCI过程具有鲁棒性，并且所提出的方法是一种实用的解决方案。