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Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Feng, Helian ; Borg, Åke LU ; Olsson, Håkan LU orcid and Ellberg, Carolina LU orcid (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)
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author
; ; and
author collaboration
organization
publishing date
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}},
}