X-chromosome is often excluded from the so called "whole-genome" association studies due to the differences it exhibits between males and females. One particular analytical challenge is the unknown status of X-inactivation, where one of the two X-chromosome variants in females may be randomly selected to be silenced. In the absence of biological evidence in favor of one specific model, we consider a Bayesian model averaging framework that offers a principled way to account for the inherent model uncertainty, providing model averaging-based posterior density intervals and Bayes factors. We examine the inferential properties of the proposed methods via extensive simulation studies, and we apply the methods to a genetic association study of an intestinal disease occurring in about 20% of cystic fibrosis patients. Compared with the results previously reported assuming the presence of inactivation, we show that the proposed Bayesian methods provide more feature-rich quantities that are useful in practice.

中文翻译：

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基因关联研究中X染色体灭活困境的贝叶斯模型平均。

由于X染色体在男性和女性之间表现出差异，因此经常被排除在所谓的“全基因组”关联研究之外。一个特定的分析挑战是X灭活的未知状态，在雌性中两个X染色体变异之一可以随机选择以使其沉默。在没有生物学证据支持一个特定模型的情况下，我们考虑一种贝叶斯模型平均框架，该框架为解决固有模型不确定性提供了一种有原则的方法，并提供了基于模型平均的后验密度区间和贝叶斯因子。我们通过广泛的模拟研究来检验所提出方法的推论性质，并将这些方法应用于大约20％的囊性纤维化患者发生肠道疾病的遗传关联研究。