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, Jennifer Stone

Research output: Contribution to journalArticle

1 Citation (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 languageEnglish
Article number1741
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Fingerprint

genome
Genome-Wide Association Study
loci
Transcriptome
breast
genes
Genes
cancer
Breast Neoplasms
Quantitative Trait Loci
Tissue
estrogens
Estrogen Receptors
adipose tissues
etiology
spleen
Gene expression
gene expression
Adipose Tissue
Blood Cells

Cite this

EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, & Stone, J. (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
EMBRACE Collaborators ; GC-HBOC Study Collaborators ; GEMO Study Collaborators ; ABCTB Investigators ; HEBON Investigators ; BCFR Investigators ; Stone, Jennifer. / Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators & Stone, J 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. / EMBRACE Collaborators; GC-HBOC Study Collaborators; GEMO Study Collaborators; ABCTB Investigators; HEBON Investigators; BCFR Investigators ; Stone, Jennifer.

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

Research output: Contribution to journalArticle

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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

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AU - Barwell, Julian

AU - Brady, Angela

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AU - Cook, Jackie

AU - Davidson, Rosemarie

AU - Donaldson, Alan

AU - Eason, Jacqueline

AU - Eeles, Ros

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AU - Gregory, Helen

AU - Hanson, Helen

AU - Henderson, Alex

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AU - Izatt, Louise

AU - Kennedy, M. John

AU - Lalloo, Fiona

AU - Miller, Clare

AU - Morrison, Patrick J.

AU - Ong, Kai ren

AU - Perkins, Jo

AU - Porteous, Mary E.

AU - Rogers, Mark T.

AU - Side, Lucy E.

AU - Snape, Katie

AU - Walker, Lisa

AU - Harrington, Patricia A.

AU - Arnold, Norbert

AU - Auber, Bernd

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AU - Borde, Julika

AU - Caliebe, Almuth

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AU - Gehrig, Andrea

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AU - Hauke, Jan

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AU - Just, Walter

AU - Kast, Karin

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AU - Lemke, Johannes

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AU - Platzer, Konrad

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AU - Weber, Bernhard H.F.

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AU - Sokolowska, Johanna

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AU - Lindström, Sara

AU - Long, Jirong

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AU - Manoochehri, Mehdi

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AU - Michailidou, Kyriaki

AU - Miller, Austin

AU - Montagna, Marco

AU - Moreno, Fernando

AU - Moserle, Lidia

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AU - Nussbaum, Robert L.

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Olsson, Håkan

AU - Osorio, Ana

AU - Papp, Janos

AU - Stone, Jennifer

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.

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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 -

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