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

Manuel A R 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 Asseryanis, Jacopo Azzollini, Judith Balmañà, Daniel R. Barnes, Daniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska & 14 others Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Ake Borg, GC-HBOC Study Collaborators, GEMO Study Collaborators, EMBRACE Collaborators, HEBON Investigators, BCFR Investigators, ABCTB Investigators, Graham Giles, Melissa Southey, Roger L. Milne

Research output: Contribution to journalArticleResearchpeer-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 languageEnglish
Article number1741
Number of pages18
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Ferreira, M. A. R., Gamazon, E. R., Al-Ejeh, F., Aittomäki, K., Andrulis, I. L., Anton-Culver, H., ... Milne, R. L. (2019). Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications, 10(1), [1741]. https://doi.org/10.1038/s41467-018-08053-5
Ferreira, Manuel A R ; Gamazon, Eric R. ; Al-Ejeh, Fares ; Aittomäki, Kristiina ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arason, Adalgeir ; Arndt, Volker ; Aronson, Kristan J. ; Arun, Banu K. ; Asseryanis, Ella ; Azzollini, Jacopo ; Balmañà, Judith ; Barnes, Daniel R. ; Barrowdale, Daniel ; Beckmann, Matthias W. ; Behrens, Sabine ; Benitez, Javier ; Bermisheva, Marina ; Białkowska, Katarzyna ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bolla, Manjeet K. ; Borg, Ake ; GC-HBOC Study Collaborators ; GEMO Study Collaborators ; EMBRACE Collaborators ; HEBON Investigators ; BCFR Investigators ; ABCTB Investigators ; Giles, Graham ; Southey, Melissa ; Milne, Roger L. / Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. In: Nature Communications. 2019 ; Vol. 10, No. 1.
@article{c3bf333b40e940589fc4b810f310e2cb,
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 = "Ferreira, {Manuel A R} 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 Białkowska and Carl Blomqvist and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bolla, {Manjeet K.} and Ake Borg and {GC-HBOC Study Collaborators} and {GEMO Study Collaborators} and {EMBRACE Collaborators} and {HEBON Investigators} and {BCFR Investigators} and {ABCTB Investigators} and Graham Giles and Melissa Southey and Milne, {Roger L.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-018-08053-5",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Ferreira, MAR, Gamazon, ER, Al-Ejeh, F, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Asseryanis, E, Azzollini, J, Balmañà, J, Barnes, DR, Barrowdale, D, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Białkowska, K, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bolla, MK, Borg, A, GC-HBOC Study Collaborators, GEMO Study Collaborators, EMBRACE Collaborators, HEBON Investigators, BCFR Investigators, ABCTB Investigators, Giles, G, Southey, M & Milne, RL 2019, 'Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer' Nature Communications, vol. 10, no. 1, 1741. https://doi.org/10.1038/s41467-018-08053-5

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. / Ferreira, Manuel A R; Gamazon, Eric R.; Al-Ejeh, Fares; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arason, Adalgeir; Arndt, Volker; Aronson, Kristan J.; Arun, Banu K.; Asseryanis, Ella; Azzollini, Jacopo; Balmañà, Judith; Barnes, Daniel R.; Barrowdale, Daniel; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Białkowska, Katarzyna; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borg, Ake; GC-HBOC Study Collaborators; GEMO Study Collaborators; EMBRACE Collaborators; HEBON Investigators; BCFR Investigators; ABCTB Investigators ; Giles, Graham; Southey, Melissa; Milne, Roger L.

In: Nature Communications, Vol. 10, No. 1, 1741, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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

AU - Ferreira, Manuel A R

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 - Balmañà, 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 - GC-HBOC Study Collaborators

AU - GEMO Study Collaborators

AU - EMBRACE Collaborators

AU - HEBON Investigators

AU - BCFR Investigators

AU - ABCTB Investigators

AU - Giles, Graham

AU - Southey, Melissa

AU - Milne, Roger L.

PY - 2019/12/1

Y1 - 2019/12/1

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 - http://www.scopus.com/inward/record.url?scp=85064432929&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-08053-5

DO - 10.1038/s41467-018-08053-5

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1741

ER -

Ferreira MAR, Gamazon ER, Al-Ejeh F, Aittomäki K, Andrulis IL, Anton-Culver H et al. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications. 2019 Dec 1;10(1). 1741. https://doi.org/10.1038/s41467-018-08053-5