Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility

Kho, Pik Fang; Wang, Xuemin; Cuellar-Partida, Gabriel; Dork, Thilo; Goode, Ellen L.; Lambrechts, Diether; Scott, Rodney J.; Spurdle, Amanda B.; O'Mara, Tracy A.; Glubb, Dylan M.

Title: Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility
Creator: Kho, Pik Fang; Wang, Xuemin; Cuellar-Partida, Gabriel; Dork, Thilo; Goode, Ellen L.; Lambrechts, Diether; Scott, Rodney J.; Spurdle, Amanda B.; O'Mara, Tracy A.; Glubb, Dylan M.
Relation: Communications Biology Vol. 4, Issue 1, no. 1211
Publisher Link: http://dx.doi.org/10.1038/s42003-021-02745-3
Publisher: Nature Publishing Group
Resource Type: journal article
Date: 2021
Description: Genome-wide association studies (GWAS) have revealed sixteen risk loci for endoemtrial cancer but the identification of candidate susceptibility genes remains challenging. Here, we perform transcriptome-wide association study (TWAS) analyses using the largest endometrial cancer GWAS and gene expression from six relevant tissues, prioritizing eight candidate endometrial cancer susceptibility genes, one of which (EEFSEC) is located at a potentially novel endometrial cancer risk locus. We also show evidence of biologically relevant tissue-specific expression associations for CYP19A1 (adipose), HEY2 (ovary) and SKAP1 (whole blood). A phenome-wide association study demonstrates associations of candidate susceptibility genes with anthropometric, cardiovascular, diabetes, bone health and sex hormone traits that are related to endometrial cancer risk factors. Lastly, analysis of TWAS data highlights candidate compounds for endometrial cancer repurposing. In summary, this study reveals endometrial cancer susceptibility genes, including those with evidence of tissue specificity, providing insights into endometrial cancer aetiology and avenues for therapeutic development.
Subject: cancer genetics; endometrial cancer; gene expression profiling; female; SDG 3; Sustainable Development Goals
Identifier: http://hdl.handle.net/1959.13/1467662
Identifier: uon:47870
Identifier: ISSN:2399-3642
Language: eng
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