XCMAX4: A Robust X Chromosomal Genetic Association Test Accounting for Covariates

Although the X chromosome accounts for about 5% of the human genes, it is routinely excluded from genome-wide association studies probably due to its unique structure and complex biological patterns. While some statistical methods have been proposed for testing the association between X chromosomal markers and diseases, very a few of them can adjust for covariates. Unfortunately, those methods that can incorporate covariates either need to specify an X chromosome inactivation model or require the permutation procedure to compute the p value. In this article, we proposed a novel analytic approach based on logistic regression that allows for covariates and does not need to specify the underlying X chromosome inactivation pattern. Simulation studies showed that our proposed method controls the size well and has robust performance in power across various practical scenarios. We applied the proposed method to analyze Graves’ disease data to show its usefulness in practice.