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MDPI, Genes, 7(13), p. 1220, 2022

DOI: 10.3390/genes13071220

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Multi-Cell-Type Openness-Weighted Association Studies for Trait-Associated Genomic Segments Prioritization

Journal article published in 2022 by Shuang Song ORCID, Hongyi Sun, Jun S. Liu ORCID, Lin Hou
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Openness-weighted association study (OWAS) is a method that leverages the in silico prediction of chromatin accessibility to prioritize genome-wide association studies (GWAS) signals, and can provide novel insights into the roles of non-coding variants in complex diseases. A prerequisite to apply OWAS is to choose a trait-related cell type beforehand. However, for most complex traits, the trait-relevant cell types remain elusive. In addition, many complex traits involve multiple related cell types. To address these issues, we develop OWAS-joint, an efficient framework that aggregates predicted chromatin accessibility across multiple cell types, to prioritize disease-associated genomic segments. In simulation studies, we demonstrate that OWAS-joint achieves a greater statistical power compared to OWAS. Moreover, the heritability explained by OWAS-joint segments is higher than or comparable to OWAS segments. OWAS-joint segments also have high replication rates in independent replication cohorts. Applying the method to six complex human traits, we demonstrate the advantages of OWAS-joint over a single-cell-type OWAS approach. We highlight that OWAS-joint enhances the biological interpretation of disease mechanisms, especially for non-coding regions.