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dc.contributor.authorWalsh, Naomi
dc.contributor.authorZhang, Han
dc.contributor.authorHyland, Paula L
dc.contributor.authorYang, Qi
dc.contributor.authorMocci, Evelina
dc.contributor.authorZhang, Mingfeng
dc.contributor.authorChilds, Erica J
dc.contributor.authorCollins, Irene
dc.contributor.authorWang, Zhaoming
dc.contributor.authorArslan, Alan A
dc.contributor.authorBeane-Freeman, Laura
dc.contributor.authorBracci, Paige M
dc.contributor.authorBrennan, Paul
dc.contributor.authorCanzian, Federico
dc.contributor.authorDuell, Eric J
dc.contributor.authorGallinger, Steven
dc.contributor.authorGiles, Graham G
dc.contributor.authorGoggins, Michael
dc.contributor.authorGoodman, Gary E
dc.contributor.authorGoodman, Phyllis J
dc.contributor.authorHung, Rayjean J
dc.contributor.authorKooperberg, Charles
dc.contributor.authorKurtz, Robert C
dc.contributor.authorMalats, Núria
dc.contributor.authorLeMarchand, Loic
dc.contributor.authorNeale, Rachel E
dc.contributor.authorOlson, Sara H
dc.contributor.authorScelo, Ghislaine
dc.contributor.authorShu, Xiao O
dc.contributor.authorVan Den Eeden, Stephen K
dc.contributor.authorVisvanathan, Kala
dc.contributor.authorWhite, Emily
dc.contributor.authorZheng, Wei
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorAndreotti, Gabriella
dc.contributor.authorBabic, Ana
dc.contributor.authorBamlet, William R
dc.contributor.authorBerndt, Sonja I
dc.contributor.authorBorgida, Ayelet
dc.contributor.authorBoutron-Ruault, Marie-Christine
dc.contributor.authorBrais, Lauren
dc.contributor.authorBrennan, Paul
dc.contributor.authorBueno-de-Mesquita, Bas
dc.contributor.authorBuring, Julie
dc.contributor.authorChaffee, Kari G
dc.contributor.authorChanock, Stephen
dc.contributor.authorCleary, Sean
dc.contributor.authorCotterchio, Michelle
dc.contributor.authorForetova, Lenka
dc.contributor.authorFuchs, Charles
dc.contributor.authorM Gaziano, J Michael
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorGoggins, Michael
dc.contributor.authorHackert, Thilo
dc.contributor.authorHaiman, Christopher
dc.contributor.authorHartge, Patricia
dc.contributor.authorHasan, Manal
dc.contributor.authorHelzlsouer, Kathy J
dc.contributor.authorHerman, Joseph
dc.contributor.authorHolcatova, Ivana
dc.contributor.authorHolly, Elizabeth A
dc.contributor.authorHoover, Robert
dc.contributor.authorHung, Rayjean J
dc.contributor.authorJanout, Vladimir
dc.contributor.authorKlein, Eric A
dc.contributor.authorKurtz, Robert C
dc.contributor.authorLaheru, Daniel
dc.contributor.authorLee, I-Min
dc.contributor.authorLu, Lingeng
dc.contributor.authorMalats, Núria
dc.contributor.authorMannisto, Satu
dc.contributor.authorMilne, Roger L
dc.contributor.authorOberg, Ann L
dc.contributor.authorOrlow, Irene
dc.contributor.authorPatel, Alpa V
dc.contributor.authorPeters, Ulrike
dc.contributor.authorPorta, Miquel
dc.contributor.authorReal, Francisco X
dc.contributor.authorRothman, Nathaniel
dc.contributor.authorSesso, Howard D
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorSilverman, Debra
dc.contributor.authorStrobel, Oliver
dc.contributor.authorSund, Malin
dc.contributor.authorThornquist, Mark D
dc.contributor.authorTobias, Geoffrey S
dc.contributor.authorWactawski-Wende, Jean
dc.contributor.authorWareham, Nick
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorWentzensen, Nicolas
dc.contributor.authorWheeler, William
dc.contributor.authorYu, Herbert
dc.contributor.authorZeleniuch-Jacquotte, Anne
dc.contributor.authorKraft, Peter
dc.contributor.authorLi, Donghui
dc.contributor.authorJacobs, Eric J
dc.contributor.authorPetersen, Gloria M
dc.contributor.authorWolpin, Brian M
dc.contributor.authorRisch, Harvey A
dc.contributor.authorAmundadottir, Laufey T
dc.contributor.authorYu, Kai
dc.contributor.authorKlein, Alison P
dc.contributor.authorStolzenberg-Solomon, Rachael Z
dc.date.accessioned2019-03-14T12:35:50Z
dc.date.available2019-03-14T12:35:50Z
dc.date.issued2018-12-12
dc.identifier.issn1460-2105
dc.identifier.pmid30541042
dc.identifier.doi10.1093/jnci/djy155
dc.identifier.urihttp://hdl.handle.net/10029/622872
dc.description.abstractGenome-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. 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. 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. 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.en_US
dc.language.isoenen_US
dc.titleAgnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.en_US
dc.typeArticleen_US
dc.identifier.journalJ Natl Cancer Inst 2019; 111(6):557-67en_US
dc.source.journaltitleJournal of the National Cancer Institute


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