TY - JOUR
T1 - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
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 - Dahlstrom, Jane
AU - Morey, Adrienne
N1 - Publisher Copyright:
© 2019, The Author(s).
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
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1741
ER -