Zhong, Jun and Jermusyk, Ashley and Wu, Lang and Hoskins, Jason W. and Collins, Irene and Mocci, Evelina and Zhang, Mingfeng and Song, Lei and Chung, Charles C. and Zhang, Tongwu and Xiao, Wenming and Albanes, Demetrius and Andreotti, Gabriella and Arslan, Alan A. and Babic, Ana and Bamlet, William R. and Beane-Freeman, Laura and Berndt, Sonja and Borgida, Ayelet and Bracci, Paige M. and Brais, Lauren and Brennan, Paul and Bueno-de-Mesquita, Bas and Buring, Julie and Canzian, Federico and Childs, Erica J. and Cotterchio, Michelle and Du, Mengmeng and Duell, Eric J. and Fuchs, Charles and Gallinger, Steven and Gaziano, J. Michael and Giles, Graham G. and Giovannucci, Edward and Goggins, Michael and Goodman, Gary E. and Goodman, Phyllis J. and Haiman, Christopher and Hartge, Patricia and Hasan, Manal and Helzlsouer, Kathy J. and Holly, Elizabeth A. and Klein, Eric A. and Kogevinas, Manolis and Kurtz, Robert J. and LeMarchand, Loic and Malats, Nuria and Mannisto, Satu and Milne, Roger and Neale, Rachel E. and Ng, Kimmie and Obazee, Ofure and Oberg, Ann L. and Orlow, Irene and Patel, Alpa and Peters, Ulrike and Porta, Miquel and Rothman, Nathaniel and Scelo, Ghislaine and Sesso, Howard D. and Severi, Gianluca and Sieri, Sabina and Silverman, Debra and Sund, Malin and Tjonneland, Anne and Thornquist, Mark D. and Tobias, Geoffrey S. and Trichopoulou, Antonia and Van den Eeden, Stephen K. and Visvanathan, Kala and Wactawski-Wende, Jean and Wentzensen, Nicolas and White, Emily and Yu, Herbert and Yuan, Chen and Zeleniuch-Jacquotte, Anne and Hoover, Robert and Brown, Kevin and Kooperberg, Charles and Risch, Harvey A. and Jacobs, Eric J. and Li, Donghui and Yu, Kai and Shu, Xiao-Ou and Chanock, Stephen J. and Wolpin, Brian M. and Stolzenberg-Solomon, Rachael Z. and Chatterjee, Nilanjan and Klein, Alison P. and Smith, Jill P. and Kraft, Peter and Shi, Jianxin and Petersen, Gloria M. and Zheng, Wei and Amundadottir, Laufey T. (2020) A transcriptome-wide association study identifies novel candidate susceptibility genes for pancreatic cancer. JNCI-Journal of The National Cancer Institute, 112 (10). ISSN 00278874, DOI https://doi.org/10.1093/jnci/djz246.
Full text not available from this repository.Abstract
Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics n = 95] and Genotype-Tissue Expression v7 n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
| Item Type: | Article |
|---|---|
| Funders: | Intramural Research Program (IRP), Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health (NIH) |
| Uncontrolled Keywords: | Databases, Genetic; Gene Expression; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Transcriptome |
| Subjects: | R Medicine > R Medicine (General) > Medical technology R Medicine > RC Internal medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 28 Oct 2024 07:07 |
| Last Modified: | 28 Oct 2024 07:07 |
| URI: | http://eprints.um.edu.my/id/eprint/36389 |
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