dc.date.accessioned | 2020-05-16T19:28:40Z | |
dc.date.available | 2020-05-16T19:28:40Z | |
dc.date.created | 2020-01-08T09:34:21Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Fagny, Maud Platig, John Kuijjer, Marieke Lydia Lin, Xihong Quackenbush, John . Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function. British Journal of Cancer. 2019 | |
dc.identifier.uri | http://hdl.handle.net/10852/75823 | |
dc.description.abstract | Background
Genome-wide association studies (GWASes) have identified many noncoding germline single-nucleotide polymorphisms (SNPs) that are associated with an increased risk of developing cancer. However, how these SNPs affect cancer risk is still largely unknown.
Methods
We used a systems biology approach to analyse the regulatory role of cancer-risk SNPs in thirteen tissues. By using data from the Genotype-Tissue Expression (GTEx) project, we performed an expression quantitative trait locus (eQTL) analysis. We represented both significant cis- and trans-eQTLs as edges in tissue-specific eQTL bipartite networks.
Results
Each tissue-specific eQTL network is organised into communities that group sets of SNPs and functionally related genes. When mapping cancer-risk SNPs to these networks, we find that in each tissue, these SNPs are significantly overrepresented in communities enriched for immune response processes, as well as tissue-specific functions. Moreover, cancer-risk SNPs are more likely to be ‘cores’ of their communities, influencing the expression of many genes within the same biological processes. Finally, cancer-risk SNPs preferentially target oncogenes and tumour-suppressor genes, suggesting that they may alter the expression of these key cancer genes.
Conclusions
This approach provides a new way of understanding genetic effects on cancer risk and provides a biological context for interpreting the results of GWAS cancer studies. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function | |
dc.type | Journal article | |
dc.creator.author | Fagny, Maud | |
dc.creator.author | Platig, John | |
dc.creator.author | Kuijjer, Marieke Lydia | |
dc.creator.author | Lin, Xihong | |
dc.creator.author | Quackenbush, John | |
cristin.unitcode | 185,57,55,0 | |
cristin.unitname | Marieke Kuijjer Group - Computational Biology and Systems Medicine | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1768224 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=British Journal of Cancer&rft.volume=&rft.spage=&rft.date=2019 | |
dc.identifier.jtitle | British Journal of Cancer | |
dc.identifier.volume | 122 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 569 | |
dc.identifier.endpage | 577 | |
dc.identifier.doi | https://doi.org/10.1038/s41416-019-0614-3 | |
dc.identifier.urn | URN:NBN:no-78843 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0007-0920 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/75823/1/2019-12-09_fagny_br_j_cancer.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | NFR/187615 | |