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Kho PF, Wang X, Cuéllar-Partida G, et al. Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility. Commun Biol. 2021;4(1):1211doi: 10.1038/s42003-021-02745-3.
Kho, P. F., Wang, X., Cuéllar-Partida, G., Dörk, T., Goode, E. L., Lambrechts, D., Scott, R. J., Spurdle, A. B., O'Mara, T. A., & Glubb, D. M. (2021). Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility. Communications biology, 4(1), 1211. https://doi.org/10.1038/s42003-021-02745-3
Kho, Pik Fang, et al. "Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility." Communications biology vol. 4,1 (2021): 1211. doi: https://doi.org/10.1038/s42003-021-02745-3
Kho PF, Wang X, Cuéllar-Partida G, Dörk T, Goode EL, Lambrechts D, Scott RJ, Spurdle AB, O'Mara TA, Glubb DM. Multi-tissue transcriptome-wide association study identifies eight candidate genes and tissue-specific gene expression underlying endometrial cancer susceptibility. Commun Biol. 2021 Oct 21;4(1):1211. doi: 10.1038/s42003-021-02745-3. PMID: 34675350; PMCID: PMC8531339.
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Commun Biol. 2021 Oct 21;4(1):1211. doi: 10.1038/s42003-021-02745-3.

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

Communications biology

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

Affiliations

  1. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  2. School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
  3. 23andMe Inc, Sunnyvale, CA, USA.
  4. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  5. Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  6. Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, VIB Center for Cancer Biology, Leuven, Belgium.
  7. Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, NSW, Australia.
  8. Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
  9. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. [email protected].

PMID: 34675350 PMCID: PMC8531339 DOI: 10.1038/s42003-021-02745-3

Abstract

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.

© 2021. The Author(s).

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