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A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

, ; , ; Wu, Lang; Shi, Wei; Long, Jirong; Guo, Xingyi; Michailidou, Kyriaki; Beesley, Jonathan; Bolla, Manjeet K. and Shu, Xiao Ou, et al. (2018) In Nature Genetics 50(7). p.968-978
Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48... (More)

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10−6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

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Nature Genetics
volume
50
issue
7
pages
968 - 978
publisher
Nature Publishing Group
external identifiers
  • scopus:85048695897
ISSN
1061-4036
DOI
10.1038/s41588-018-0132-x
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English
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yes
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09fa405b-2621-4c16-bf29-0da6ec4158b3
date added to LUP
2018-06-28 13:12:10
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2019-02-20 11:21:06
@article{09fa405b-2621-4c16-bf29-0da6ec4158b3,
  abstract     = {<p>The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P &lt; 5.82 × 10<sup>−6</sup>, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.</p>},
  author       = {,  and ,  and Wu, Lang and Shi, Wei and Long, Jirong and Guo, Xingyi and Michailidou, Kyriaki and Beesley, Jonathan and Bolla, Manjeet K. and Shu, Xiao Ou and Lu, Yingchang and Cai, Qiuyin and Al-Ejeh, Fares and Rozali, Esdy and Wang, Qin and Dennis, Joe and Li, Bingshan and Zeng, Chenjie and Feng, Helian and Gusev, Alexander and Barfield, Richard T. and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Auer, Paul L. and Barrdahl, Myrto and Baynes, Caroline and Beckmann, Matthias W. and Benitez, Javier and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Brinton, Louise and Broberg, Per and Brucker, Sara Y. and Burwinkel, Barbara and Caldés, Trinidad and Canzian, Federico and Carter, Brian D. and Castelao, J. Esteban and Chang-Claude, Jenny and Chen, Xiaoqing and Cheng, Ting Yuan David and Christiansen, Hans and Clarke, Christine L. and Collée, Margriet and Humphreys, Keith and Olsson, Håkan},
  issn         = {1061-4036},
  language     = {eng},
  number       = {7},
  pages        = {968--978},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer},
  url          = {http://dx.doi.org/10.1038/s41588-018-0132-x},
  volume       = {50},
  year         = {2018},
}