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dc.contributor.authorLu, Yen_US
dc.contributor.authorBeeghly-Fadiel, Aen_US
dc.contributor.authorWu, Len_US
dc.contributor.authorGuo, Xen_US
dc.contributor.authorLi, Ben_US
dc.contributor.authorSchildkraut, JMen_US
dc.contributor.authorIm, HKen_US
dc.contributor.authorChen, YAen_US
dc.contributor.authorPermuth, JBen_US
dc.contributor.authorReid, BMen_US
dc.contributor.authorTeer, JKen_US
dc.contributor.authorMoysich, KBen_US
dc.contributor.authorAndrulis, ILen_US
dc.contributor.authorAnton-Culver, Hen_US
dc.contributor.authorArun, BKen_US
dc.contributor.authorBandera, EVen_US
dc.contributor.authorBarkardottir, RBen_US
dc.contributor.authorBarnes, DRen_US
dc.contributor.authorBenitez, Jen_US
dc.contributor.authorBjorge, Len_US
dc.contributor.authorBrenton, Jen_US
dc.contributor.authorButzow, Ren_US
dc.contributor.authorCaldes, Ten_US
dc.contributor.authorCaligo, MAen_US
dc.contributor.authorCampbell, Ien_US
dc.contributor.authorChang-Claude, Jen_US
dc.contributor.authorClaes, KBMen_US
dc.contributor.authorCouch, FJen_US
dc.contributor.authorCramer, DWen_US
dc.contributor.authorDaly, MBen_US
dc.contributor.authordeFazio, Aen_US
dc.contributor.authorDennis, Jen_US
dc.contributor.authorDiez, Oen_US
dc.contributor.authorDomchek, SMen_US
dc.contributor.authorDörk, Ten_US
dc.contributor.authorEaston, DFen_US
dc.contributor.authorEccles, DMen_US
dc.contributor.authorFasching, PAen_US
dc.contributor.authorFortner, RTen_US
dc.contributor.authorFountzilas, Gen_US
dc.contributor.authorFriedman, Een_US
dc.contributor.authorGanz, PAen_US
dc.contributor.authorGarber, Jen_US
dc.contributor.authorGiles, GGen_US
dc.contributor.authorGodwin, AKen_US
dc.contributor.authorGoldgar, DEen_US
dc.contributor.authorGoodman, MTen_US
dc.contributor.authorGreene, MHen_US
dc.contributor.authorGronwald, Jen_US
dc.contributor.authorHamann, Uen_US
dc.contributor.authorHeitz, Fen_US
dc.contributor.authorHildebrandt, MATen_US
dc.contributor.authorHøgdall, CKen_US
dc.contributor.authorHollestelle, Aen_US
dc.contributor.authorHulick, PJen_US
dc.contributor.authorHuntsman, DGen_US
dc.contributor.authorImyanitov, ENen_US
dc.contributor.authorIsaacs, Cen_US
dc.contributor.authorJakubowska, Aen_US
dc.contributor.authorJames, Pen_US
dc.contributor.authorKarlan, BYen_US
dc.contributor.authorKelemen, LEen_US
dc.contributor.authorKiemeney, LAen_US
dc.contributor.authorKjaer, SKen_US
dc.contributor.authorKwong, Aen_US
dc.contributor.authorLe, NDen_US
dc.contributor.authorLeslie, Gen_US
dc.contributor.authorLesueur, Fen_US
dc.contributor.authorLevine, DAen_US
dc.contributor.authorMattiello, Aen_US
dc.contributor.authorMay, Ten_US
dc.contributor.authorMcGuffog, Len_US
dc.contributor.authorMcNeish, IAen_US
dc.contributor.authorMerritt, MAen_US
dc.contributor.authorModugno, Fen_US
dc.contributor.authorMontagna, Men_US
dc.contributor.authorNeuhausen, SLen_US
dc.contributor.authorNevanlinna, Hen_US
dc.contributor.authorNielsen, FCen_US
dc.contributor.authorNikitina-Zake, Len_US
dc.contributor.authorNussbaum, RLen_US
dc.contributor.authorOffit, Ken_US
dc.contributor.authorOlah, Een_US
dc.contributor.authorOlopade, OIen_US
dc.contributor.authorOlson, SHen_US
dc.contributor.authorOlsson, Hen_US
dc.contributor.authorOsorio, Aen_US
dc.contributor.authorPark, SKen_US
dc.contributor.authorParsons, MTen_US
dc.contributor.authorPeeters, PHMen_US
dc.contributor.authorPejovic, Ten_US
dc.contributor.authorPeterlongo, Pen_US
dc.contributor.authorPhelan, CMen_US
dc.contributor.authorPujana, MAen_US
dc.contributor.authorRamus, SJen_US
dc.contributor.authorRennert, Gen_US
dc.contributor.authorRisch, Hen_US
dc.contributor.authorRodriguez, GCen_US
dc.contributor.authorRodríguez-Antona, Cen_US
dc.contributor.authorRomieu, Ien_US
dc.contributor.authorRookus, MAen_US
dc.contributor.authorRossing, MAen_US
dc.contributor.authorRzepecka, IKen_US
dc.contributor.authorSandler, DPen_US
dc.contributor.authorSchmutzler, RKen_US
dc.contributor.authorSetiawan, VWen_US
dc.contributor.authorSharma, Pen_US
dc.contributor.authorSieh, Wen_US
dc.contributor.authorSimard, Jen_US
dc.contributor.authorSinger, CFen_US
dc.contributor.authorSong, Hen_US
dc.contributor.authorSouthey, MCen_US
dc.contributor.authorSpurdle, ABen_US
dc.contributor.authorSutphen, Ren_US
dc.contributor.authorSwerdlow, AJen_US
dc.contributor.authorTeixeira, MRen_US
dc.contributor.authorTeo, SHen_US
dc.contributor.authorThomassen, Men_US
dc.contributor.authorTischkowitz, Men_US
dc.contributor.authorToland, AEen_US
dc.contributor.authorTrichopoulou, Aen_US
dc.contributor.authorTung, Nen_US
dc.contributor.authorTworoger, SSen_US
dc.contributor.authorvan Rensburg, EJen_US
dc.contributor.authorVanderstichele, Aen_US
dc.contributor.authorVega, Aen_US
dc.contributor.authorEdwards, DVen_US
dc.contributor.authorWebb, PMen_US
dc.contributor.authorWeitzel, JNen_US
dc.contributor.authorWentzensen, Nen_US
dc.contributor.authorWhite, Een_US
dc.contributor.authorWolk, Aen_US
dc.contributor.authorWu, AHen_US
dc.contributor.authorYannoukakos, Den_US
dc.contributor.authorZorn, KKen_US
dc.contributor.authorGayther, SAen_US
dc.contributor.authorAntoniou, ACen_US
dc.contributor.authorBerchuck, Aen_US
dc.contributor.authorGoode, ELen_US
dc.contributor.authorChenevix-Trench, Gen_US
dc.contributor.authorSellers, TAen_US
dc.contributor.authorPharoah, PDPen_US
dc.contributor.authorZheng, Wen_US
dc.contributor.authorLong, Jen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-04T15:50:49Z
dc.date.issued2018-09-15en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30054336en_US
dc.identifier0008-5472.CAN-18-0951en_US
dc.identifier.citationCancer Res, 2018, 78 (18), pp. 5419 - 5430en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3045
dc.identifier.eissn1538-7445en_US
dc.identifier.doi10.1158/0008-5472.CAN-18-0951en_US
dc.description.abstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10-6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.en_US
dc.format.extent5419 - 5430en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleA Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-07-24en_US
rioxxterms.versionofrecord10.1158/0008-5472.CAN-18-0951en_US
rioxxterms.licenseref.startdate2018-09-15en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Resen_US
pubs.issue18en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublisheden_US
pubs.volume78en_US
pubs.embargo.termsNot knownen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US


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