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

EMBRACE Collaborators; GC-HBOC Study Collaborators; GEMO Study Collaborators; ABCTB Investigators; HEBON Investigators; BCFR Investigators

doi:10.1038/s41467-018-08053-5

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

EMBRACE Collaborators
, GC-HBOC Study Collaborators
, GEMO Study Collaborators
, ABCTB Investigators
, HEBON Investigators
, BCFR Investigators

University of Cambridge
Centre for Cancer Genetic Epidemiology
GEMO study: Cancer Genetics Network “Groupe Génétique et Cancer”
Department of Tumour Biology
Service de Génétique
UNICANCER Genetic Group
Australian Breast Cancer Tissue Bank
Hereditary Breast and Ovarian Cancer Research Group
Queensland Institute of Medical Research
Vanderbilt University
Helsinki University Hospital
University of Toronto
University of California at Irvine
Landspitali University Hospital
University of Iceland
German Cancer Research Center
Queen's University Kingston
University of Texas MD Anderson Cancer Center
Medical University of Vienna
Fondazione IRCCS Istituto Nazionale dei Tumori
Vall d'Hebron Institute of Oncology
Friedrich-Alexander University Erlangen-Nürnberg
Center for Biomedical Network Research on Rare Diseases (CIBERER)
Biomedical Network on Rare Diseases (CIBERER)
Russian Academy of Sciences
Pomeranian Medical University in Szczecin
Örebro University
Hannover Medical School
N.N. Alexandrov Research Institute of Oncology and Medical Radiology
University of Copenhagen
Lund University
Robert Bosch Foundation
University of Tübingen
Antoni van Leeuwenhoek Hospital
Heidelberg University
Hospital Clínico San Carlos de Madrid
University of Pisa
Peter Maccallum Cancer Centre
University of Melbourne
University of Sydney
American Cancer Society
Instituto de Investigacion Sanitaria Galicia Sur (IISGS)
University of Hamburg
National Institutes of Health
Columbia University
Ghent University
Leeds Teaching Hospitals NHS Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
University Hospitals of Leicester NHS Trust
London North West University Healthcare NHS Trust
Royal Devon & Exeter NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

93 Scopus citations

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.

Original language	English
Article number	1741
Pages (from-to)	1741
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08053-5
State	Published - Apr 15 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Breast Neoplasms/genetics
Female
Gene Expression Profiling
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Quantitative Trait Loci

Access to Document

10.1038/s41467-018-08053-5

Cite this

@article{9d8259f65c1449ecbc406bff37bf348e,

title = "Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer",

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.",

keywords = "Breast Neoplasms/genetics, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Quantitative Trait Loci",

author = "\{EMBRACE Collaborators\} and \{GC-HBOC Study Collaborators\} and \{GEMO Study Collaborators\} and \{ABCTB Investigators\} and \{HEBON Investigators\} and \{BCFR Investigators\} and Ferreira, \{Manuel A.\} and Gamazon, \{Eric R.\} and Fares Al-Ejeh and Kristiina Aittom{\"a}ki and Andrulis, \{Irene L.\} and Hoda Anton-Culver and Adalgeir Arason and Volker Arndt and Aronson, \{Kristan J.\} and Arun, \{Banu K.\} and Ella Asseryanis and Jacopo Azzollini and Judith Balma{\~n}a and Barnes, \{Daniel R.\} and Daniel Barrowdale and Beckmann, \{Matthias W.\} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Katarzyna Bia{\l}kowska and Carl Blomqvist and Bogdanova, \{Natalia V.\} and Bojesen, \{Stig E.\} and Bolla, \{Manjeet K.\} and Ake Borg and Hiltrud Brauch and Hermann Brenner and Annegien Broeks and Barbara Burwinkel and Trinidad Cald{\'e}s and Caligo, \{Maria A.\} and Daniele Campa and Ian Campbell and Federico Canzian and Jonathan Carter and Carter, \{Brian D.\} and Castelao, \{Jose E.\} and Jenny Chang-Claude and Chanock, \{Stephen J.\} and Hans Christiansen and Chung, \{Wendy K.\} and Claes, \{Kathleen B.M.\} and Clarke, \{Christine L.\} and Julian Adlard and Munaza Ahmed and Julian Barwell and Angela Brady and Carole Brewer and Daly, \{Mary B.\}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = apr,

day = "15",

doi = "10.1038/s41467-018-08053-5",

language = "English",

volume = "10",

pages = "1741",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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TY - JOUR

T1 - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

AU - EMBRACE Collaborators

AU - GC-HBOC Study Collaborators

AU - GEMO Study Collaborators

AU - ABCTB Investigators

AU - HEBON Investigators

AU - BCFR Investigators

AU - Ferreira, Manuel A.

AU - Gamazon, Eric R.

AU - Al-Ejeh, Fares

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arason, Adalgeir

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Arun, Banu K.

AU - Asseryanis, Ella

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barnes, Daniel R.

AU - Barrowdale, Daniel

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Białkowska, Katarzyna

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Borg, Ake

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Burwinkel, Barbara

AU - Caldés, Trinidad

AU - Caligo, Maria A.

AU - Campa, Daniele

AU - Campbell, Ian

AU - Canzian, Federico

AU - Carter, Jonathan

AU - Carter, Brian D.

AU - Castelao, Jose E.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Christiansen, Hans

AU - Chung, Wendy K.

AU - Claes, Kathleen B.M.

AU - Clarke, Christine L.

AU - Adlard, Julian

AU - Ahmed, Munaza

AU - Barwell, Julian

AU - Brady, Angela

AU - Brewer, Carole

AU - Daly, Mary B.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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.

AB - 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.

KW - Breast Neoplasms/genetics

KW - Female

KW - Gene Expression Profiling

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Quantitative Trait Loci

UR - https://www.scopus.com/pages/publications/85064432929

U2 - 10.1038/s41467-018-08053-5

DO - 10.1038/s41467-018-08053-5

M3 - Article

C2 - 30988301

AN - SCOPUS:85064432929

SN - 2041-1723

VL - 10

SP - 1741

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1741

ER -

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

Abstract

UN SDGs

Keywords

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