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

Division of Evolution, Infection and Genomics

QIMR Berghofer Medical Research Institute
Vanderbilt University
University of Cambridge
Helsinki University Central Hospital (HUCH)
Mount Sinai Hospital of University of Toronto
University of Toronto
University of California, Irvine
Landspitali University Hospital
University of Iceland
DKFZ (Deutsches Krebsforschungszentrum Heidelberg)
Queens University at Kingston
University of Texas MD Anderson Cancer Center
Comprehensive Cancer Center
Fondazione IRCCS
Vall D'Hebron Institute of Oncology
Friedrich-Alexander Universitat Erlangen Nurnberg
Centro de Investigación en Red de Enfermedades Raras (CIBERER)
Spanish National Cancer Research Centre
Ufa Scientific Center RAS
Pomeranian Medical University
Orebro University
Medizinische Hochschule Hannover (Hannover Medical School)
N.N. Alexandrov Research Institute of Oncology and Medical Radiology
Copenhagen University Hospital
University of Copenhagen
Lund University
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
University of Tübingen
Netherlands Cancer Institute
University Womens Clinic Heidelberg
IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
University of Sydney
Royal Devon & Exeter NHS Foundation Trust
Sheffield Children's Hospital
University of Glasgow
University of Aberdeen
Newcastle-upon-Tyne Hospitals NHS Foundation Trust
The University of London
University of Dublin Trinity College
Birmingham Women's and Children's NHS Foundation Trust
University Hospital of Wales
Fox Chase Cancer Centre
Karolinska Institutet
University of Queensland
University of Melbourne
Parkville Familial Cancer Centre
The Institute of Cancer Research (University of London)
Ohio State University
Vanderbilt-Ingram Cancer Center

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

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
Early online date	15 Apr 2019
DOIs	https://doi.org/10.1038/s41467-018-08053-5
Publication status	Published - 2019

UN SDGs

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

SDG 3 Good Health and Well-being

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10.1038/s41467-018-08053-5

Cite this

@article{a4512f6eee0b460b96dac8156fba5188,

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 Jonathan Carter and Carole Brewer and Jackie Cook and Rosemarie Davidson and Evans, \{D. Gareth\} and Helen Gregory and Alex Henderson and Shirley Hodgson and Kennedy, \{M. John\} and Ong, \{Kai ren\} and Rogers, \{Mark T.\} and Daly, \{Mary B.\} and Wei He and Peter Simpson and Senno Verhoef and James, \{Paul A.\} and Jones, \{Michael E.\} and Singer, \{Christian F.\} and Toland, \{Amanda E.\} and Wei Zheng",

year = "2019",

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

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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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 - Carter, Jonathan

AU - Brewer, Carole

AU - Cook, Jackie

AU - Davidson, Rosemarie

AU - Evans, D. Gareth

AU - Gregory, Helen

AU - Henderson, Alex

AU - Hodgson, Shirley

AU - Kennedy, M. John

AU - Ong, Kai ren

AU - Rogers, Mark T.

AU - Daly, Mary B.

AU - He, Wei

AU - Simpson, Peter

AU - Verhoef, Senno

AU - James, Paul A.

AU - Jones, Michael E.

AU - Singer, Christian F.

AU - Toland, Amanda E.

AU - Zheng, Wei

PY - 2019

Y1 - 2019

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.

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

U2 - 10.1038/s41467-018-08053-5

DO - 10.1038/s41467-018-08053-5

M3 - Article

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

Abstract

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