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dc.contributor.author | Tworoger, Shelley S. | en_US |
dc.contributor.author | van Altena, Anne M. | en_US |
dc.contributor.author | Van Nieuwenhuysen, Els | en_US |
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dc.contributor.author | Vierkant, Robert A. | en_US |
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dc.contributor.author | Walsh, Christine | en_US |
dc.contributor.author | Wentzensen, Nicolas | en_US |
dc.contributor.author | Whittemore, Alice S. | en_US |
dc.contributor.author | Wicklund, Kristine G. | en_US |
dc.contributor.author | Wilkens, Lynne R. | en_US |
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dc.contributor.author | Wu, Anna H. | en_US |
dc.contributor.author | Yang, Hannah | en_US |
dc.contributor.author | Zheng, Wei | en_US |
dc.contributor.author | Ziogas, Argyrios | en_US |
dc.contributor.author | Monteiro, Alvaro | en_US |
dc.contributor.author | Pharoah, Paul D. | en_US |
dc.contributor.author | Gayther, Simon A. | en_US |
dc.contributor.author | Freedman, Matthew L. | en_US |
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dc.date.accessioned | 2016-08-02T12:35:32Z | |
dc.date.available | 2016-08-02T12:35:32Z | |
dc.date.issued | 2015-09-22 | |
dc.Published | Nature Communications 2015, 6:8234 | eng |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://hdl.handle.net/1956/12394 | |
dc.description.abstract | Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4 × 10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10−10 for risk variants (P<10−4) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC. | en_US |
dc.language.iso | eng | eng |
dc.publisher | Nature Publishing Group | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | eng |
dc.title | Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2016-04-11T08:46:39Z | |
dc.description.version | publishedVersion | en_US |
dc.identifier.doi | https://doi.org/10.1038/ncomms9234 | |
dc.identifier.cristin | 1282475 | |