A novel model for the X-chromosome inactivation association on survival data

Author:

Han Dongxiao1,Hao Meiling2ORCID,Qu Lianqiang3,Xu Wei4

Affiliation:

1. Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China

2. School of Statistics, University of International Business and Economics, Beijing, China

3. School of Mathematics and Statistics, Central China Normal University, Wuhan, China

4. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

Abstract

The X-linked genetic association is overlooked in most of the genetic studies because of the complexity of X-chromosome inactivation process. In fact, the biological process of the gene at the same locus can vary across different subjects. Besides, the skewness of X-chromosome inactivation is inherently subject-specific (even tissue-specific within subjects) and cannot be accurately represented by a population-level parameter. To tackle this issue, a new model is proposed to incorporate the X-linked genetic association into right-censored survival data. The novel model can present that the X-linked genes on different subjects may go through different biological processes via a mixed distribution. Further, a random effect is employed to describe the uncertainty of the biological process for every subject. The proposed method can derive the probability for the escape of X-chromosome inactivation and derive the unbiased estimates of the model parameters. The Legendre–Gauss Quadrature method is used to approximate the integration over the random effect. Finite sample performance of this method is examined via extensive simulation studies. An application is illustrated with the implementation on a cancer genetic study with right-censored survival data.

Funder

Canadian Institutes of Health Research

Fundamental Research Funds for the Central Universities in UIBE

Publisher

SAGE Publications

Subject

Health Information Management,Statistics and Probability,Epidemiology

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