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

Department of Genetics and Computational Biology
Queensland Institute of Medical Research
Vanderbilt Genetic Institute
Vanderbilt University
University of Cambridge
Department of Clinical Genetics
Helsinki University Hospital
Fred A. Litwin Center for Cancer Genetics
University of Toronto
Department of Epidemiology
University of California at Irvine
Department of Pathology
Landspitali University Hospital
University of Iceland
German Cancer Research Center
Queen's University Kingston
Department of Breast Medical Oncology
University of Texas MD Anderson Cancer Center
Dept of OB/GYN and Comprehensive Cancer Center
Medical University of Vienna
Unit of Medical Genetics
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Oncogenetics Group
Vall d'Hebron Institute of Oncology
Department of Medical Oncology
Centre for Cancer Genetic Epidemiology
Department of Gynaecology and Obstetrics
Friedrich-Alexander University Erlangen-Nürnberg
Division of Cancer Epidemiology
Centro de Investigación en Red de Enfermedades Raras (CIBERER)
Human Cancer Genetics Program
Spanish National Cancer Research Centre
Russian Academy of Sciences
Department of Genetics and Pathology
Pomeranian Medical University in Szczecin
Department of Oncology
Örebro University
Department of Radiation Oncology
Hannover Medical School
Gynaecology Research Unit
N.N. Alexandrov Research Institute of Oncology and Medical Radiology
Copenhagen General Population Study
University of Copenhagen
Department of Clinical Biochemistry
Department of Oncology
Lund University
Robert Bosch Foundation
University of Tübingen
Division of Preventive Oncology
Division of Molecular Pathology
Antoni van Leeuwenhoek Hospital
Molecular Epidemiology Group
Molecular Biology of Breast Cancer
Heidelberg University
Molecular Oncology Laboratory
Hospital Clínico San Carlos de Madrid
Section of Molecular Genetics
University Hospital of Pisa
Department of Biology
University of Pisa
Research Department
Peter Maccallum Cancer Centre
University of Melbourne
Genomic Epidemiology Group
Department of Gynaecological Oncology
The University of Sydney
Behavioral and Epidemiology Research Group
American Cancer Society
Oncology and Genetics Unit
Instituto de Investigacion Sanitaria Galicia Sur (IISGS)
Cancer Epidemiology Group
University of Hamburg
Division of Cancer Epidemiology and Genetics
National Institutes of Health
Departments of Pediatrics and Medicine
Columbia University
Ghent University
Yorkshire Regional Genetics Service
Leeds Teaching Hospitals NHS Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Leicestershire Clinical Genetics Service
University Hospitals of Leicester NHS Trust
North West Thames Regional Genetics Service
London North West University Healthcare NHS Trust
Department of Clinical Genetics
Royal Devon & Exeter NHS Foundation Trust
Sheffield Clinical Genetics Service
Sheffield Children's NHS Foundation Trust
Department of Clinical Genetics
South Glasgow University Hospitals

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

94 Citations (Scopus)

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
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08053-5
Publication status	Published - 1 Dec 2019
Externally published	Yes

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10.1038/s41467-018-08053-5

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@article{3024655e61564286a4b97dc0b3f8e08f,

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.",

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 Jackie Cook and Rosemarie Davidson",

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

year = "2019",

month = dec,

day = "1",

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

language = "English",

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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 - Cook, Jackie

AU - Davidson, Rosemarie

PY - 2019/12/1

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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.

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DO - 10.1038/s41467-018-08053-5

M3 - Article

C2 - 30988301

AN - SCOPUS:85064432929

SN - 2041-1723

VL - 10

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

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