| Title: |
Transcriptome-wide association study of breast cancer risk by estrogen-receptor status |
| Authors: |
GEMO Study Collaborators; EMBRACE Collaborators; GC-HBOC Study Collaborators; ABCTB Investigators; HEBON Investigators; BCFR Investigators; OCGN Investigators; Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Aittomäki, Kristiina; Blomqvist, Carl; Dunning, Alison M.; Kiiski, Johanna I.; Muranen, Taru A.; Nevanlinna, Heli; Zheng, Wei |
| Contributors: |
Medicum; Research Programs Unit; ATG - Applied Tumor Genomics; HUSLAB; Department of Medical and Clinical Genetics; HUS Shared Group Services; University of Helsinki; HUS Comprehensive Cancer Center; Department of Oncology; Clinicum; INDIVIDRUG - Individualized Drug Therapy; HUS Gynecology and Obstetrics; Department of Obstetrics and Gynecology; Biosciences |
| Publisher Information: |
Wiley-Liss Inc. |
| Publication Year: |
2020 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Cancers; Genetics; developmental biology; physiology; breast cancer subtype; causal gene; GWAS; TWAS; VARIANTS; STATISTICS; TISSUE; SUSCEPTIBILITY LOCI; IDENTIFICATION; CARRIERS; EXPRESSION |
| Description: |
Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
RIS: urn:0AE2539A2847EF6B1263807D484D9FF0; https://hdl.handle.net/10138/318533; 000517111500001 |
| Availability: |
https://hdl.handle.net/10138/318533 |
| Rights: |
unspecified ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.A0471ECE |
| Database: |
BASE |