Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.
(2020) In Genetic Epidemiology 44(5). p.442-468- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/08511034-a1ea-45fe-98bd-19bda152247c
- author
- Feng, Helian ; Borg, Åke LU ; Olsson, Håkan LU and Ellberg, Carolina LU
- author collaboration
- organization
- publishing date
- 2020-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Genetic Epidemiology
- volume
- 44
- issue
- 5
- pages
- 27 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:32115800
- pmid:32115800
- scopus:85081379482
- ISSN
- 0741-0395
- DOI
- 10.1002/gepi.22288
- language
- English
- LU publication?
- yes
- id
- 08511034-a1ea-45fe-98bd-19bda152247c
- date added to LUP
- 2020-03-13 17:06:27
- date last changed
- 2022-04-18 21:03:14
@article{08511034-a1ea-45fe-98bd-19bda152247c, abstract = {{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.}}, author = {{Feng, Helian and Borg, Åke and Olsson, Håkan and Ellberg, Carolina}}, issn = {{0741-0395}}, language = {{eng}}, number = {{5}}, pages = {{442--468}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Genetic Epidemiology}}, title = {{Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.}}, url = {{http://dx.doi.org/10.1002/gepi.22288}}, doi = {{10.1002/gepi.22288}}, volume = {{44}}, year = {{2020}}, }