eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma
| العنوان: | eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma |
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| المؤلفون: | Wang, Xiaoyu, Gharahkhani, Puya, Levine, David M., Fitzgerald, Rebecca C., Gockel, Ines, Corley, Douglas A., Risch, Harvey A., Bernstein, Leslie, Chow, Wong-Ho, Onstad, Lynn, Shaheen, Nicholas J., Lagergren, Jesper, Hardie, Laura J., Wu, Anna H., Pharoah, Paul D.P., Liu, Geoffrey, Anderson, Lesley A., Iyer, Prasad G., Gammon, Marilie D., Caldas, Carlos, Ye, Weimin, Barr, Hugh, Moayyedi, Paul, Harrison, Rebecca, Watson, R.G. Peter, Attwood, Stephen, Chegwidden, Laura, Love, Sharon B., MacDonald, David, deCaestecker, John, Prenen, Hans, Ott, Katja, Moebus, Susanne, Venerito, Marino, Lang, Hauke, Mayershofer, Rupert, Knapp, Michael, Veits, Lothar, Gerges, Christian, Weismüller, Josef, Reeh, Matthias, Nöthen, Markus, Izbicki, Jakob R., Manner, Hendrik, Neuhaus, Horst, Rösch, Thomas, Böhmer, Anne C., Hölscher, Arnulf H., Anders, Mario, Pech, Oliver, Schumacher, Brigitte, Schmidt, Claudia, Schmidt, Thomas, Noder, Tania, Lorenz, Dietmar, Vieth, Michael, May, Andrea, Hess, Timo, Kreuser, Nicole, Becker, Jessica, Ell, Christian, Tomlinson, Ian, Palles, Claire, Jankowski, Janusz A., Whiteman, David C., MacGregor, Stuart, Schumacher, Johannes, Vaughan, Thomas L., Buas, Matthew F., Dai, James Y., DeCaestecker, John, Weismueller, Josef, Noethen, Markus M., Roesch, Thomas, Boehmer, Anne C., Hoelscher, Arnulf H. |
| المصدر: | Cancer Epidemiology, Biomarkers & Prevention, 31, 1735-1745 Cancer epidemiology, biomarkers and prevention Cancer Epidemiology, Biomarkers & Prevention, 31, 9, pp. 1735-1745 Cancer Epidemiol Biomarkers Prev |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Barrett Esophagus, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Oncology, Esophageal Neoplasms, Epidemiology, Quantitative Trait Loci, Medizin, Humans, Genetic Predisposition to Disease, Human medicine, Adenocarcinoma, Biology, Article |
| الوصف: | Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. Results: Although the standard approach did not identify significant signals, the eQTL set–based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set–based genetic association approach. Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set–based genetic association approach as an alternative method for TWAS analysis. |
| وصف الملف: | application/pdf |
| تدمد: | 1055-9965 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36d3d842a36edd40a765388897f866d6Test http://hdl.handle.net/2066/288033Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....36d3d842a36edd40a765388897f866d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10559965 |
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