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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Wu, Lang 
Shi, Wei 
Long, Jirong 
Michailidou, Kyriaki 

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 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.

Description

Keywords

Breast Neoplasms, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk, Transcriptome

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

50

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (16565)
National Cancer Institute (U19CA148065)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (A16563)
Cancer Research UK (A10118)
Cancer Research UK (A10710)