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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Author

Listed:
  • Manuel A. Ferreira

    (QIMR Berghofer Medical Research Institute)

  • Eric R. Gamazon

    (Vanderbilt University
    University of Cambridge)

  • Fares Al-Ejeh

    (QIMR Berghofer Medical Research Institute)

  • Kristiina Aittomäki

    (University of Helsinki)

  • Irene L. Andrulis

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
    University of Toronto)

  • Hoda Anton-Culver

    (University of California Irvine)

  • Adalgeir Arason

    (Landspitali University Hospital
    University of Iceland)

  • Volker Arndt

    (German Cancer Research Center (DKFZ))

  • Kristan J. Aronson

    (Queen’s University)

  • Banu K. Arun

    (University of Texas MD Anderson Cancer Center)

  • Ella Asseryanis

    (Medical University of Vienna)

  • Jacopo Azzollini

    (Fondazione IRCCS Istituto Nazionale dei Tumori (INT))

  • Judith Balmaña

    (Vall dHebron Institute of Oncology (VHIO)
    University Hospital)

  • Daniel R. Barnes

    (University of Cambridge)

  • Daniel Barrowdale

    (University of Cambridge)

  • Matthias W. Beckmann

    (Friedrich-Alexander-University Erlangen-Nuremberg)

  • Sabine Behrens

    (German Cancer Research Center (DKFZ))

  • Javier Benitez

    (Centro de Investigación en Red de Enfermedades Raras (CIBERER)
    Spanish National Cancer Research Centre (CNIO))

  • Marina Bermisheva

    (Ufa Federal Research Centre of Russian Academy of Sciences)

  • Katarzyna Białkowska

    (Pomeranian Medical University)

  • Carl Blomqvist

    (University of Helsinki
    Örebro University Hospital)

  • Natalia V. Bogdanova

    (Hannover Medical School
    Hannover Medical School
    N.N. Alexandrov Research Institute of Oncology and Medical Radiology)

  • Stig E. Bojesen

    (Herlev and Gentofte Hospital, Copenhagen University Hospital
    Copenhagen University Hospital
    University of Copenhagen)

  • Manjeet K. Bolla

    (University of Cambridge)

  • Ake Borg

    (Lund University and Skåne University Hospital)

  • Hiltrud Brauch

    (Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
    University of Tübingen
    German Cancer Research Center (DKFZ))

  • Hermann Brenner

    (German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Annegien Broeks

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Barbara Burwinkel

    (German Cancer Research Center (DKFZ)
    University Womens Clinic Heidelberg, University of Heidelberg)

  • Trinidad Caldés

    (IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos))

  • Maria A. Caligo

    (University Hospital of Pisa)

  • Daniele Campa

    (German Cancer Research Center (DKFZ)
    University of Pisa)

  • Ian Campbell

    (Peter MacCallum Cancer Center
    The University of Melbourne)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Jonathan Carter

    (Chris O’Brien Lifehouse and The University of Sydney)

  • Brian D. Carter

    (American Cancer Society)

  • Jose E. Castelao

    (Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS)

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Medical Center Hamburg-Eppendorf)

  • Stephen J. Chanock

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Hans Christiansen

    (Hannover Medical School)

  • Wendy K. Chung

    (Columbia University)

  • Kathleen B. M. Claes

    (Ghent University)

  • Christine L. Clarke

    (University of Sydney)

  • Fergus J. Couch

    (Mayo Clinic)

  • Angela Cox

    (University of Sheffield)

  • Simon S. Cross

    (University of Sheffield)

  • Kamila Czene

    (Karolinska Institutet)

  • Mary B. Daly

    (Fox Chase Cancer Center)

  • Miguel Hoya

    (IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos))

  • Joe Dennis

    (University of Cambridge)

  • Peter Devilee

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Orland Diez

    (Vall dHebron Institute of Oncology (VHIO)
    University Hospital Vall dHebron)

  • Thilo Dörk

    (Hannover Medical School)

  • Alison M. Dunning

    (University of Cambridge)

  • Miriam Dwek

    (University of Westminster)

  • Diana M. Eccles

    (University of Southampton)

  • Bent Ejlertsen

    (Copenhagen University Hospital)

  • Carolina Ellberg

    (Lund University)

  • Christoph Engel

    (University of Leipzig)

  • Mikael Eriksson

    (Karolinska Institutet)

  • Peter A. Fasching

    (Friedrich-Alexander-University Erlangen-Nuremberg
    University of California at Los Angeles)

  • Olivia Fletcher

    (The Institute of Cancer Research)

  • Henrik Flyger

    (Copenhagen University Hospital)

  • Eitan Friedman

    (Chaim Sheba Medical Center
    Tel Aviv University)

  • Debra Frost

    (University of Cambridge)

  • Marike Gabrielson

    (Karolinska Institutet)

  • Manuela Gago-Dominguez

    (Complejo Hospitalario Universitario de Santiago, SERGAS
    University of California San Diego)

  • Patricia A. Ganz

    (Jonsson Comprehensive Cancer Centre, UCLA)

  • Susan M. Gapstur

    (American Cancer Society)

  • Judy Garber

    (Dana-Farber Cancer Institute)

  • Montserrat García-Closas

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services
    Institute of Cancer Research)

  • José A. García-Sáenz

    (Centro Investigación Biomédica en Red de Cáncer (CIBERONC))

  • Mia M. Gaudet

    (American Cancer Society)

  • Graham G. Giles

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Gord Glendon

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital)

  • Andrew K. Godwin

    (Kansas University Medical Center)

  • Mark S. Goldberg

    (McGill University
    McGill University)

  • David E. Goldgar

    (University of Utah School of Medicine)

  • Anna González-Neira

    (Spanish National Cancer Research Centre (CNIO))

  • Mark H. Greene

    (National Cancer Institute)

  • Jacek Gronwald

    (Pomeranian Medical University)

  • Pascal Guénel

    (University Paris-Saclay)

  • Christopher A. Haiman

    (University of Southern California)

  • Per Hall

    (Karolinska Institutet
    Södersjukhuset)

  • Ute Hamann

    (German Cancer Research Center (DKFZ))

  • Wei He

    (Karolinska Institutet)

  • Jane Heyworth

    (The University of Western Australia)

  • Frans B. L. Hogervorst

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital)

  • Antoinette Hollestelle

    (Erasmus MC Cancer Institute)

  • Robert N. Hoover

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • John L. Hopper

    (The University of Melbourne)

  • Peter J. Hulick

    (NorthShore University HealthSystem
    The University of Chicago Pritzker School of Medicine)

  • Keith Humphreys

    (Karolinska Institutet)

  • Evgeny N. Imyanitov

    (N.N. Petrov Institute of Oncology. St.)

  • Claudine Isaacs

    (Georgetown University)

  • Milena Jakimovska

    (Macedonian Academy of Sciences and Arts)

  • Anna Jakubowska

    (Pomeranian Medical University
    Pomeranian Medical University)

  • Paul A. James

    (The University of Melbourne
    Peter MacCallum Cancer Center)

  • Ramunas Janavicius

    (Vilnius University Hospital Santariskiu Clinics)

  • Rachel C. Jankowitz

    (University of Pittsburgh School of Medicine)

  • Esther M. John

    (Stanford University School of Medicine)

  • Nichola Johnson

    (The Institute of Cancer Research)

  • Vijai Joseph

    (Memorial Sloan-Kettering Cancer Center)

  • Beth Y. Karlan

    (University of California at Los Angeles)

  • Elza Khusnutdinova

    (Ufa Federal Research Centre of Russian Academy of Sciences
    Bashkir State Medical University)

  • Johanna I. Kiiski

    (Helsinki University Hospital, University of Helsinki)

  • Yon-Dschun Ko

    (Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus)

  • Michael E. Jones

    (The Institute of Cancer Research)

  • Irene Konstantopoulou

    (National Centre for Scientific Research ‘Demokritos’)

  • Vessela N. Kristensen

    (Oslo University Hospital-Radiumhospitalet
    University of Oslo)

  • Yael Laitman

    (Chaim Sheba Medical Center)

  • Diether Lambrechts

    (VIB Center for Cancer Biology, VIB
    University of Leuven)

  • Conxi Lazaro

    (ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC)

  • Goska Leslie

    (University of Cambridge)

  • Jenny Lester

    (University of California at Los Angeles)

  • Fabienne Lesueur

    (Genetic Epidemiology of Cancer team, Inserm U900
    Institut Curie
    Mines ParisTech)

  • Sara Lindström

    (University of Washington School of Public Health
    Fred Hutchinson Cancer Research Center)

  • Jirong Long

    (Vanderbilt University School of Medicine)

  • Jennifer T. Loud

    (National Cancer Institute)

  • Jan Lubiński

    (Pomeranian Medical University)

  • Enes Makalic

    (The University of Melbourne)

  • Arto Mannermaa

    (University of Eastern Finland
    University of Eastern Finland
    Kuopio University Hospital)

  • Mehdi Manoochehri

    (German Cancer Research Center (DKFZ))

  • Sara Margolin

    (Södersjukhuset
    Södersjukhuset, Karolinska Institutet)

  • Tabea Maurer

    (University Medical Center Hamburg-Eppendorf)

  • Dimitrios Mavroudis

    (University Hospital of Heraklion)

  • Lesley McGuffog

    (University of Cambridge)

  • Alfons Meindl

    (University of Munich, Campus Großhadern)

  • Usha Menon

    (University College London)

  • Kyriaki Michailidou

    (University of Cambridge
    The Cyprus Institute of Neurology & Genetics)

  • Austin Miller

    (Roswell Park Cancer Institute)

  • Marco Montagna

    (Veneto Institute of Oncology IOV - IRCCS)

  • Fernando Moreno

    (Centro Investigación Biomédica en Red de Cáncer (CIBERONC))

  • Lidia Moserle

    (Veneto Institute of Oncology IOV - IRCCS)

  • Anna Marie Mulligan

    (University of Toronto
    University Health Network)

  • Katherine L. Nathanson

    (University of Pennsylvania)

  • Susan L. Neuhausen

    (Beckman Research Institute of City of Hope)

  • Heli Nevanlinna

    (Helsinki University Hospital, University of Helsinki)

  • Ines Nevelsteen

    (University Hospitals Leuven)

  • Finn C. Nielsen

    (Copenhagen University Hospital)

  • Liene Nikitina-Zake

    (Latvian Biomedical Research and Study Centre)

  • Robert L. Nussbaum

    (University of California San Francisco)

  • Kenneth Offit

    (Memorial Sloan-Kettering Cancer Center
    Memorial Sloan-Kettering Cancer Center)

  • Edith Olah

    (National Institute of Oncology)

  • Olufunmilayo I. Olopade

    (The University of Chicago)

  • Håkan Olsson

    (Lund University)

  • Ana Osorio

    (Centro de Investigación en Red de Enfermedades Raras (CIBERER)
    Spanish National Cancer Research Centre (CNIO))

  • Janos Papp

    (National Institute of Oncology)

  • Tjoung-Won Park-Simon

    (Hannover Medical School)

  • Michael T. Parsons

    (QIMR Berghofer Medical Research Institute)

  • Inge Sokilde Pedersen

    (Aalborg University Hospital
    Aalborg University Hospital
    Aalborg University)

  • Ana Peixoto

    (Portuguese Oncology Institute)

  • Paolo Peterlongo

    (Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology)

  • Paul D. P. Pharoah

    (University of Cambridge
    University of Cambridge)

  • Dijana Plaseska-Karanfilska

    (Macedonian Academy of Sciences and Arts)

  • Bruce Poppe

    (Ghent University)

  • Nadege Presneau

    (University of Westminster)

  • Paolo Radice

    (Fondazione IRCCS Istituto Nazionale dei Tumori (INT))

  • Johanna Rantala

    (Karolinska Institutet)

  • Gad Rennert

    (Carmel Medical Center and Technion Faculty of Medicine)

  • Harvey A. Risch

    (Yale School of Public Health)

  • Emmanouil Saloustros

    (University Hospital of Larissa)

  • Kristin Sanden

    (City of Hope Clinical Cancer Genetics Community Research Network)

  • Elinor J. Sawyer

    (Guy’s Hospital, King’s College London)

  • Marjanka K. Schmidt

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital)

  • Rita K. Schmutzler

    (University of Cologne
    University of Cologne)

  • Priyanka Sharma

    (University of Kansas Medical Center)

  • Xiao-Ou Shu

    (Vanderbilt University School of Medicine)

  • Jacques Simard

    (Centre Hospitalier Universitaire de Québec – Université Laval, Research Center)

  • Christian F. Singer

    (Medical University of Vienna)

  • Penny Soucy

    (Centre Hospitalier Universitaire de Québec – Université Laval, Research Center)

  • Melissa C. Southey

    (Monash University
    The University of Melbourne)

  • John J. Spinelli

    (BC Cancer
    University of British Columbia)

  • Amanda B. Spurdle

    (QIMR Berghofer Medical Research Institute)

  • Jennifer Stone

    (The University of Melbourne
    Curtin University and University of Western Australia)

  • Anthony J. Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • William J. Tapper

    (University of Southampton)

  • Jack A. Taylor

    (NIH
    National Institute of Environmental Health Sciences, NIH)

  • Manuel R. Teixeira

    (Portuguese Oncology Institute
    University of Porto)

  • Mary Beth Terry

    (Columbia University)

  • Alex Teulé

    (IDIBELL (Bellvitge Biomedical Research Institute),Catalan Institute of Oncology, CIBERONC)

  • Mads Thomassen

    (Odense University Hospital)

  • Kathrin Thöne

    (University Medical Center Hamburg-Eppendorf)

  • Darcy L. Thull

    (University of Pittsburgh School of Medicine)

  • Marc Tischkowitz

    (McGill University
    University of Cambridge)

  • Amanda E. Toland

    (The Ohio State University)

  • Diana Torres

    (German Cancer Research Center (DKFZ)
    Pontificia Universidad Javeriana)

  • Thérèse Truong

    (University Paris-Saclay)

  • Nadine Tung

    (Beth Israel Deaconess Medical Center)

  • Celine M. Vachon

    (Mayo Clinic)

  • Christi J. Asperen

    (Leiden University Medical Center)

  • Ans M. W. Ouweland

    (Erasmus University Medical Center)

  • Elizabeth J. Rensburg

    (University of Pretoria)

  • Ana Vega

    (CIBERER, IDIS)

  • Alessandra Viel

    (Centro di Riferimento Oncologico di Aviano (CRO), IRCCS)

  • Qin Wang

    (University of Cambridge)

  • Barbara Wappenschmidt

    (University of Cologne
    University of Cologne)

  • Jeffrey N. Weitzel

    (Clinical Cancer Genomics, City of Hope)

  • Camilla Wendt

    (Södersjukhuset, Karolinska Institutet)

  • Robert Winqvist

    (University of Oulu
    Northern Finland Laboratory Centre Oulu)

  • Xiaohong R. Yang

    (Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services)

  • Drakoulis Yannoukakos

    (National Centre for Scientific Research ‘Demokritos’)

  • Argyrios Ziogas

    (University of California Irvine)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Antonis C. Antoniou

    (University of Cambridge)

  • Wei Zheng

    (Vanderbilt University School of Medicine)

  • Douglas F. Easton

    (University of Cambridge
    University of Cambridge)

  • Roger L. Milne

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Jonathan Beesley

    (QIMR Berghofer Medical Research Institute)

  • Georgia Chenevix-Trench

    (QIMR Berghofer Medical Research Institute)

Abstract

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Suggested Citation

  • Manuel A. Ferreira & Eric R. Gamazon & Fares Al-Ejeh & Kristiina Aittomäki & Irene L. Andrulis & Hoda Anton-Culver & Adalgeir Arason & Volker Arndt & Kristan J. Aronson & Banu K. Arun & Ella Asseryani, 2019. "Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08053-5
    DOI: 10.1038/s41467-018-08053-5
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