FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.
FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.
复制标题
DOI：
10.1002/gepi.21979
复制
发表时间：
2016-09
影响因子：
2.1
通讯作者：
Won S
中科院分区：
文献类型：
--
作者：
Choi S;Lee S;Qiao D;Hardin M;Cho MH;Silverman EK;Park T;Won S
尽管X染色体有许多与人类疾病功能相关的基因，但X染色体复杂的生物学特性阻碍了有效的遗传关联分析，并且仅报道了少数与复杂性状显着相关的X连锁变异。例如，X连锁基因的剂量补偿通常是通过使雌性中每个X连锁变体中的一个等位基因失活来实现的。然而，一些 X 连锁变异可以逃避这种 X 染色体失活。如果事先不了解 X 连锁变异的基因表达过程，就无法进行有效的遗传分析，并且错误指定的信息可能会导致功率损失。在本报告中，我们提出了新的统计方法，用于对基于家族的样本进行二分表型的罕见 X 连锁变异遗传关联分析。所提出的方法计算效率高，可以在几个小时内完成 X 连锁分析。模拟研究证明了所提出方法的统计效率，然后将其应用于慢性阻塞性肺疾病（COPD）X染色体的稀有变异关联分析。一些有希望的重要 X 连锁基因被鉴定出来，说明了所提出的方法的实际重要性。
Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods.