Pathway-based genetic association analysis for overdispersed count data

© 2025 Informa UK Limited, trading as Taylor & Francis Group.

Détails bibliographiques
Publié dans:Journal of applied statistics. - 1991. - 52(2025), 12 vom: 03., Seite 2306-2320
Auteur principal: Liu, Yang (Auteur)
Format: Article en ligne
Langue:English
Publié: 2025
Accès à la collection:Journal of applied statistics
Sujets:Journal Article Overdispersion association analysis mixed effects negative binomial regression somatic mutations
Description
Résumé:© 2025 Informa UK Limited, trading as Taylor & Francis Group.
Overdispersion is a common phenomenon in genetic data, such as gene expression count data. In genetic association studies, it is important to investigate the association between a gene expression and a set of genetic variants from a pathway. However, existing approaches for pathway analysis are primarily designed for continuous and binary outcomes and are not applicable to overdispersed count data. In this paper, we propose a hierarchical approach to analyze the association between an overdispersed count response and a set of low-frequency genetic variants in negative binomial regression. We derive score-type test statistics for both fixed and random effects of genetic variants, and further introduce a novel procedure for efficiently combining these two statistics for global testing. Through simulation studies, we demonstrate that the proposed method tends to be more powerful than existing methods under a wide range of scenarios. Additionally, we apply the proposed method to a colorectal cancer study, demonstrating its power in identifying associations between gene expression and somatic mutations
Description:Date Revised 10.09.2025
published: Electronic-eCollection
Citation Status In-Process
ISSN:0266-4763
DOI:10.1080/02664763.2025.2460073