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

Title: Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
Authors: GC-HBOC Study Collaborators; GEMO Study Collaborators; EMBRACE Collaborators; HEBON Investigators; BCFR Investigators; ABCTB Investigators; Ferreira, Manuel A.; Gamazon, Eric R.; Aittomäki, Kristiina; Blomqvist, Carl; Kiiski, Johanna I.; Nevanlinna, Heli
Contributors: Department of Medical and Clinical Genetics; Kristiina Aittomäki / Principal Investigator; Clinicum; Medicum; Department of Oncology; Department of Obstetrics and Gynecology; HUS Comprehensive Cancer Center
Publisher Information: Nature Publishing Group
Publication Year: 2019
Collection: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
Subject Terms: CYCLIN E2; VARIANTS; EXPRESSION; ENHANCERS; CHROMATIN; DISEASE; AUTOIMMUNITY; REGULATOR; COMPLEX; CELLS; Biomedicine
Description: 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. ; Peer reviewed
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://hdl.handle.net/10138/301535; 000464494100010
Availability: https://hdl.handle.net/10138/301535
Rights: cc_by ; info:eu-repo/semantics/openAccess ; openAccess
Accession Number: edsbas.94CDDC1
Database: BASE