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The Capital Region of Denmark - a part of Copenhagen University Hospital
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

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  1. Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma

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  2. A large-cohort, longitudinal study determines pre-cancer disease routes across different cancer types

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  3. Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk

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  4. Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia

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  5. The Balance Players of the Adaptive Immune System

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  1. Shared heritability and functional enrichment across six solid cancers

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  2. Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina

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  3. A Comprehensive Gene-Environment Interaction Analysis in Ovarian Cancer using Genome-wide Significant Common Variants

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  4. Risk of cardiovascular events in men treated for prostate cancer compared with prostate cancer-free men

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  • Yingchang Lu
  • Alicia Beeghly-Fadiel
  • Lang Wu
  • Xingyi Guo
  • Bingshan Li
  • Joellen M Schildkraut
  • Hae Kyung Im
  • Yian A Chen
  • Jennifer B Permuth
  • Brett M Reid
  • Jamie K Teer
  • Kirsten B Moysich
  • Irene L Andrulis
  • Hoda Anton-Culver
  • Banu K Arun
  • Elisa V Bandera
  • Rosa B Barkardottir
  • Daniel R Barnes
  • Javier Benitez
  • Line Bjorge
  • James Brenton
  • Ralf Butzow
  • Trinidad Caldes
  • Maria A Caligo
  • Ian Campbell
  • Jenny Chang-Claude
  • Kathleen B M Claes
  • Fergus J Couch
  • Daniel W Cramer
  • Mary B Daly
  • Anna deFazio
  • Joe Dennis
  • Orland Diez
  • Susan M Domchek
  • Thilo Dörk
  • Douglas F Easton
  • Diana M Eccles
  • Peter A Fasching
  • Renée T Fortner
  • George Fountzilas
  • Eitan Friedman
  • Patricia A Ganz
  • Judy Garber
  • Graham G Giles
  • Andrew K Godwin
  • David E Goldgar
  • Marc T Goodman
  • Mark H Greene
  • Jacek Gronwald
  • Ute Hamann
  • Florian Heitz
  • Michelle A T Hildebrandt
  • Claus K Høgdall
  • Antoinette Hollestelle
  • Peter J Hulick
  • David G Huntsman
  • Evgeny N Imyanitov
  • Claudine Isaacs
  • Anna Jakubowska
  • Paul James
  • Beth Y Karlan
  • Linda E Kelemen
  • Lambertus A Kiemeney
  • Susanne K Kjaer
  • Ava Kwong
  • Nhu D Le
  • Goska Leslie
  • Fabienne Lesueur
  • Douglas A Levine
  • Amalia Mattiello
  • Taymaa May
  • Lesley McGuffog
  • Iain A McNeish
  • Melissa A Merritt
  • Francesmary Modugno
  • Marco Montagna
  • Susan L Neuhausen
  • Heli Nevanlinna
  • Finn C Nielsen
  • Liene Nikitina-Zake
  • Robert L Nussbaum
  • Kenneth Offit
  • Edith Olah
  • Olufunmilayo I Olopade
  • Sara H Olson
  • Håkan Olsson
  • Ana Osorio
  • Sue K Park
  • Michael T Parsons
  • Petra H M Peeters
  • Tanja Pejovic
  • Paolo Peterlongo
  • Catherine M Phelan
  • Miquel Angel Pujana
  • Susan J Ramus
  • Gad Rennert
  • Harvey Risch
  • Gustavo C Rodriguez
  • Cristina Rodríguez-Antona
  • Isabelle Romieu
  • Matti A Rookus
  • Mary Anne Rossing
  • Iwona K Rzepecka
  • Dale P Sandler
  • Rita K Schmutzler
  • Veronica W Setiawan
  • Priyanka Sharma
  • Weiva Sieh
  • Jacques Simard
  • Christian F Singer
  • Honglin Song
  • Melissa C Southey
  • Amanda B Spurdle
  • Rebecca Sutphen
  • Anthony J Swerdlow
  • Manuel R Teixeira
  • Soo H Teo
  • Mads Thomassen
  • Marc Tischkowitz
  • Amanda E Toland
  • Antonia Trichopoulou
  • Nadine Tung
  • Shelley S Tworoger
  • Elizabeth J van Rensburg
  • Adriaan Vanderstichele
  • Ana Vega
  • Digna Velez Edwards
  • Penelope M Webb
  • Jeffrey N Weitzel
  • Nicolas Wentzensen
  • Emily White
  • Alicja Wolk
  • Anna H Wu
  • Drakoulis Yannoukakos
  • Kristin K Zorn
  • Simon A Gayther
  • Antonis C Antoniou
  • Andrew Berchuck
  • Ellen L Goode
  • Georgia Chenevix-Trench
  • Thomas A Sellers
  • Paul D P Pharoah
  • Wei Zheng
  • Jirong Long
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Large-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.

Original languageEnglish
JournalCancer Research
Volume78
Issue number18
Pages (from-to)5419-5430
Number of pages12
ISSN0008-5472
DOIs
Publication statusPublished - 15 Sep 2018

ID: 55849691