Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/18539
Título
Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.
Autor(es)
Walsh, Naomi | Zhang, Han | Hyland, Paula L | Yang, Qi | Mocci, Evelina | Zhang, Mingfeng | Childs, Erica J | Collins, Irene | Wang, Zhaoming | Arslan, Alan A | Beane-Freeman, Laura | Bracci, Paige M | Brennan, Paul | Canzian, Federico | Duell, Eric J | Gallinger, Steven | Giles, Graham G | Goggins, Michael | Goodman, Gary E | Goodman, Phyllis J | Hung, Rayjean J | Kooperberg, Charles | Kurtz, Robert C | Malats, Nuria CNIO | LeMarchand, Loic | Neale, Rachel E | Olson, Sara H | Scelo, Ghislaine | Shu, Xiao O | Van Den Eeden, Stephen K | Visvanathan, Kala | White, Emily | Zheng, Wei | Albanes, Demetrius | Andreotti, Gabriella | Babic, Ana | Bamlet, William R | Berndt, Sonja I | Borgida, Ayelet | Boutron-Ruault, Marie-Christine | Brais, Lauren | Bueno-de-Mesquita, Bas | Buring, Julie | Chaffee, Kari G | Chanock, Stephen | Cleary, Sean | Cotterchio, Michelle | Foretova, Lenka | Fuchs, Charles | M Gaziano, J Michael | Giovannucci, Edward | Hackert, Thilo | Haiman, Christopher | Hartge, Patricia | Hasan, Manal | Helzlsouer, Kathy J | Herman, Joseph | Holcatova, Ivana | Holly, Elizabeth A | Hoover, Robert | Janout, Vladimir | Klein, Eric A | Laheru, Daniel | Lee, I-Min | Lu, Lingeng | Mannisto, Satu | Milne, Roger L | Oberg, Ann L | Orlow, Irene | Patel, Alpa V | Peters, Ulrike | Porta, Miquel | Real, Francisco X | Rothman, Nathaniel | Sesso, Howard D | Severi, Gianluca | Silverman, Debra | Strobel, Oliver | Sund, Malin | Thornquist, Mark D | Tobias, Geoffrey S | Wactawski-Wende, Jean | Wareham, Nick | Weiderpass, Elisabete | Wentzensen, Nicolas | Wheeler, William | Yu, Herbert | Zeleniuch-Jacquotte, Anne | Kraft, Peter | Li, Donghui | Jacobs, Eric J | Petersen, Gloria M | Wolpin, Brian M | Risch, Harvey A | Amundadottir, Laufey T | Yu, Kai | Klein, Alison P | Stolzenberg-Solomon, Rachael Z
Fecha de publicación
2019-06-01
Cita
J Natl Cancer Inst . 2019 ;111(6):557-567.
Idioma
Inglés
Tipo de documento
journal article
Resumen
BACKGROUND
Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.
METHODS
We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.
RESULTS
We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.
CONCLUSION
Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
MESH
Carcinoma, Pancreatic Ductal | Case-Control Studies | Genetic Predisposition to Disease | Genome-Wide Association Study | Humans | Models, Statistical | Pancreatic Neoplasms | Polymorphism, Single Nucleotide
Versión en línea
DOI
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