The Sequence Kernel Association Test (SKAT) and its extensions are the most popular methods for studying the association between phenotypes and a set of single nucleotide polymorphisms. Their practical application is very wide, but most of these methods aredesigned for continuous and binary phenotypes. Ordered categorical phenotypes are also very common in practice, so there is an urgent needto develop SKAT-type tests for proportional odds model.

Results: To accommodate ordered categorical phenotypes, we propose a test named the Sequence Kernel Association Test for theProportional Odds Model (POM-SKAT). It constructs a score test for the variance of the coefficients of interest using a quasi-likelihood and theP-value is evaluated by approximating the asymptotic distribution of the test statistic with the Pearson Type III distribution. Simulation studiesdemonstrate that our method performs well and achieves high power in detecting gene-phenotype associations. We apply POM-SKAT to rheumatoid arthritis data provided by Genetic Analysis Workshop 16, identifying multiple relevant gene variants.

Publication:

Automatica Volume 164, June 2024

https://doi.org/10.1016/j.automatica.2024.111622

Author:

Liying Bao

Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China

University of Chinese Academy of Sciences, Beijing 100049, China

Civil Aviation University of China, Tianjin 300300, China

Email:baoliying@amss.ac.cn

Bo Qi

Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China

University of Chinese Academy of Sciences, Beijing 100049, China

Corresponding author at: Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China.

Email:qibo@amss.ac.cn

Daoyi Dong

School of Engineering, Australian National University, Canberra, ACT 2601 Australia

Email:Daoyi.Dong@anu.edu.au