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

• DOI: 10.1038/s42003-021-02745-3
• Publication Date: 2021-10-21T10:04:42Z
• Authors: Pik Fang Kho; Xuemin Wang; Gabriel Cuéllar-P...; Thilo Dörk; Ellen L. Goode; Diether Lambrechts; Rodney J. Scott; Amanda B. Spurdle; Tracy A. O’Mara; Dylan M. Glubb
• Keywords: Candidate gene; Genome-wide Association Study; Genetic Association

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 study (TWAS) analyses using largest endometrial GWAS and gene expression from six relevant tissues, prioritizing eight genes, one which (EEFSEC) is located at a potentially novel locus. We also show evidence biologically tissue-specific associations CYP19A1 (adipose), HEY2 (ovary) SKAP1 (whole blood). A phenome-wide demonstrates with anthropometric, cardiovascular, diabetes, bone health sex hormone traits that are related to factors. Lastly, analysis TWAS data highlights compounds repurposing. In summary, this reveals including those tissue specificity, providing insights into aetiology avenues therapeutic development.