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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk
Cancer Research, Volume 78, No. 18, Year 2018
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Description
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 ¼ 5.08, P ¼ 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. © 2018 American Association for Cancer Research.
Authors & Co-Authors
Lu, Yingchang
United States, Nashville
Vanderbilt University School of Medicine
Beeghly-Fadiel, Alicia
United States, Nashville
Vanderbilt University School of Medicine
Guo, Xingyi
United States, Nashville
Vanderbilt University School of Medicine
Li, Bingshan
United States, Nashville
Vanderbilt University Medical Center
Schildkraut, Joellen M.
United States, Charlottesville
University of Virginia
Im, Hae-kyung
United States, Chicago
The University of Chicago
Permuth, Jennifer B.
United States, Tampa
Moffitt Cancer Center
Moysich, Kirsten Barbara
United States, Buffalo
Roswell Park Cancer Institute
Andrulis, Irene L.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
Anton-Culver, Hoda
United States, Irvine
University of California, Irvine
Arun, Banu K.
United States, Houston
The University of Texas Md Anderson Cancer Center
Bandera, E. V.
United States, New Brunswick
Rutgers Cancer Institute of new Jersey
Barkardóttir, Rósa Björk
Iceland, Reykjavik
Landspitali - the National University Hospital of Iceland
Iceland, Reykjavik
Haskoli Islands
Barnes, Daniel R.
United Kingdom, Cambridge
University of Cambridge
Benit́ez, Javier J.
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Björge, Line
Norway, Bergen
Universitetet I Bergen
Brenton, James D.
United Kingdom, Cambridge
Cancer Research uk Cambridge Institute
Bützow, Ralf C.
Finland, Helsinki
Helsinki University Hospital
Caldés, Trinidad
Spain, Madrid
Centro de Investigación Biomédica en Red de Cáncer
Caligo, Maria Adelaide
Italy, Pisa
Azienda Ospedaliero Universitaria Pisana
Campbell, I. G. G.
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
University of Melbourne
Chang-Claude, Jenny C.
Germany, Heidelberg
German Cancer Research Center
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Claes, Kathleen B.M.
Belgium, Ghent
Universiteit Gent
Couch, Fergus J.
United States, Rochester
Mayo Clinic
Cramer, Daniel William
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard T.h. Chan School of Public Health
Daly, Mary B.
United States, Philadelphia
Fox Chase Cancer Center
DeFazio, Anna
Australia, Parramatta
The Westmead Institute for Medical Research
Australia, Sydney
Westmead Hospital
Dennis, Joe G.
United Kingdom, Cambridge
University of Cambridge
Díez, Orland
Spain, Barcelona
Vall D‘hebron Institut de Oncologia
Domchek, Susan M.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
d'Adamo, Adamo P.
United Kingdom, Cambridge
University of Cambridge
Eccles, Diana M.
United Kingdom, Southampton
University of Southampton, Faculty of Medicine
Fasching, Peter Andreas
United States, Los Angeles
University of California, Los Angeles
Fortner, Renée Turzanski
Germany, Heidelberg
German Cancer Research Center
Fountzilas, George
Greece, Thessaloniki
Papageorgiou General Hospital
Friedman, Eitan A.
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Israel, Tel Aviv-yafo
Tel Aviv University
Ganz, Patricia A.
United States, Los Angeles
University of California, Los Angeles
Garber, Judy Ellen
United States, Boston
Dana-farber Cancer Institute
Giles, Graham G.
Australia, East Melbourne
Cancer Council Victoria
Australia, Melbourne
University of Melbourne
Australia, Clayton
Monash University
Godwin, Andrew K.
United States, Kansas City
University of Kansas Medical Center
Goldgar, David F.
United States, Salt Lake City
University of Utah School of Medicine
Goodman, Marc T.
United States, Los Angeles
Cedars-sinai Medical Center
Greene, Mark H.
United States, Rockville
National Cancer Institute Nci
Gronwald, Jacek
Poland, Szczecin
Pomeranian Medical University in Szczecin
Hamann, Ute
Germany, Heidelberg
German Cancer Research Center
Hogdall, Claus Kim
Denmark, Copenhagen
Rigshospitalet
Hollestelle, Antoinette
Netherlands, Rotterdam
Erasmus Mc Cancer Institute
Hulick, Peter J.
United States, Evanston
Northshore University Healthsystem
United States, Chicago
Pritzker School of Medicine
Huntsman, David G.
Canada, Vancouver
British Columbia Cancer Agency
Canada, Vancouver
The University of British Columbia
Imyanitov, Evgeny N.
Russian Federation, Saint Petersburg
N.n. Petrov Research Institute of Oncology of the Ussr Ministry of Health
Isaacs, Claudine J.D.
United States, Washington, D.c.
Georgetown University
Jakubowska, Anna
Poland, Szczecin
Pomeranian Medical University in Szczecin
James, Paul A.
Australia, Melbourne
Peter Maccallum Cancer Centre
Karlan, Beth Y.
United States, Los Angeles
Cedars-sinai Medical Center
Kelemen, Linda E.
United States, Charleston
Medical University of South Carolina
Kiemeney, Lambertus A.L.M.
Netherlands, Nijmegen
Radboud Universiteit
Kjaer, Susanne Krûger
Denmark, Copenhagen
Kræftens Bekæmpelse
Denmark, Copenhagen
Rigshospitalet
Kwong, Ava
Hong Kong, Hong Kong
The University of Hong Kong
China, Hong Kong
Hong Kong Sanatorium and Hospital
Le, Nhu D.
Canada, Vancouver
British Columbia Cancer Agency
Leslie, Goska
United Kingdom, Cambridge
University of Cambridge
Lesueur, Fabienne El Khoury
France, Paris
Cancer et Génome : Bioinformatique, Biostatistiques et Épidémiologie Des Systèmes Complexes
France, Paris
Institut Curie
France, Paris
Université Psl
France, Paris
Mines Paris - Psl
Levine, Douglas A.
United States, New York
Memorial Sloan-kettering Cancer Center
United States, New York
Nyu Langone Health
McGuffog, Lesley
United Kingdom, Cambridge
University of Cambridge
Modugno, Francesmary
United States, Pittsburgh
Upmc Hillman Cancer Center
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
United States, Pittsburgh
University of Pittsburgh School of Medicine
Montagna, Marco
Italy, Padua
Istituto Oncologico Veneto Iov - Irccs
Floris, Giuseppe L.
United States, Duarte
City of Hope National Med Center
Nevanlinna, Heli A.
Finland, Helsinki
Helsinki University Hospital
Nielsen, Finn Cilius
Denmark, Copenhagen
Copenhagen University Hospital
Nussbaum, Robert L.
United States, San Francisco
University of California, San Francisco
Offit, Kenneth E.
United States, New York
Memorial Sloan-kettering Cancer Center
Oláh, Edith
Hungary, Budapest
Országos Onkológiai Intézet Budapest
Olopade, Olufunmilayo Ibironke
United States, Chicago
The University of Chicago
Osorio, Ana
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Park, Suekyung
South Korea, Seoul
Seoul National University College of Medicine
South Korea, Seoul
Seoul National University
Parsons, Michael T.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Pejović, Tanja
United States, Portland
Oregon Health & Science University
Peterlongo, Paolo
Italy, Milan
Fondazione Ifom Istituto Firc Di Oncologia Molecolare
Phelan, Catherine M.
United States, Tampa
Moffitt Cancer Center
Pujana, Miguel Àngel G.
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Ramus, Susan J.
Australia, Sydney
Unsw Sydney
Australia, Sydney
The Kinghorn Cancer Centre
Rennert, Gad
Israel, Haifa
Carmel Medical Center
Risch, Harvey A.
United States, New Haven
Yale University
Rodríguez, Gustavo C.
United States, Chicago
The University of Chicago
Rodríguez-Antona, Cristina R.
Spain, Madrid
Centro Nacional de Investigaciones Oncológicas
Romieu, Isabelle
France, Lyon
Centre International de Recherche Sur le Cancer
Rookus, Matti A.
Netherlands, Amsterdam
The Netherlands Cancer Institute
Rossing, Mary Anne
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Sandler, Dale P.
United States, Bethesda
National Institutes of Health Nih
Schmutzler, Rita Katharina
Germany, Koln
Uniklinik Köln
Germany, Koln
Universität zu Köln
Setiawan, Veronica Wendy
United States, Los Angeles
University of Southern California
Sharma, Priyanka
United States, Kansas City
University of Kansas Medical Center
Sieh, Weiva
United States, New York
Icahn School of Medicine at Mount Sinai
Simard, Jacques
Canada, Quebec
Université Laval
Singer, Christian Fridolin
Austria, Vienna
Medizinische Universität Wien
Song, Honglin
United Kingdom, Cambridge
University of Cambridge
Southey, Melissa Caroline
Australia, Melbourne
University of Melbourne
Spurdle, Amanda B.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Swerdlow, Anthony J.
United Kingdom, London
The Institute of Cancer Research
Teixeira, Manuel Rodrigues
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Portugal, Porto
Universidade do Porto
Teo, Soo Hwang
Malaysia, Kuala Lumpur
University of Malaya Medical Centre
Thomassen, Mads Christella L.G.D.
Denmark, Odense
Odense Universitetshospital
Tischkowitz, Marc D.
Canada, Montreal
Université Mcgill
United Kingdom, Cambridge
University of Cambridge
Toland, Amanda Ewart
United States, Columbus
The Ohio State University
Trichopoulou, Antonia D.
Greece, Athens
Hellenic Health Foundation, Athens
Greece, Athens
School of Medicine
Tung, Nadine M.
United States, Boston
Beth Israel Deaconess Medical Center
Tworoger, Shelley S.
United States, Tampa
Moffitt Cancer Center
United States, Boston
Harvard T.h. Chan School of Public Health
van Rensburg, Elizabeth J.
South Africa, Pretoria
University of Pretoria
Vanderstichele, Adriaan
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Vega, Ana Karina
Unknown Affiliation
Edwards, Digna R.Velez
United States, Nashville
Vanderbilt University
Webb, Penelope M.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Weitzel, Jeffrey Nelson
United States, Duarte
City of Hope National Med Center
Wentzensen, Nicolas A.
United States, Rockville
National Cancer Institute Nci
Wolk, Alicja
Sweden, Stockholm
Karolinska Institutet
Wu, Anna H.
United States, Los Angeles
University of Southern California
Yannoukakos, Drakoulis
Greece, Athens
National Centre for Scientific Research Demokritos
Zorn, Kristin K.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Gayther, Simon A.
United States, Los Angeles
University of Southern California
United States, Los Angeles
Cedars-sinai Medical Center
Antoniou, Antonis C.
United Kingdom, Cambridge
University of Cambridge
Berchuck, Andrew
United States, Durham
Duke University Medical Center
Goode, Ellen L.
United States, Rochester
Mayo Clinic
Chenevix-Trench, Georgia
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Sellers, Thomas
United States, Tampa
Moffitt Cancer Center
Pharoah, Paul D.P.
United Kingdom, Cambridge
University of Cambridge
Zheng, Wei
United States, Nashville
Vanderbilt University School of Medicine
Long, Jirong
United States, Nashville
Vanderbilt University School of Medicine
United States, Nashville
Vanderbilt University
Statistics
Citations: 39
Authors: 126
Affiliations: 124
Identifiers
Doi:
10.1158/0008-5472.CAN-18-0951
ISSN:
00085472
Research Areas
Cancer
Genetics And Genomics
Participants Gender
Female