Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma
Abstract Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating syst...
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Nature Portfolio
2021
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oai:doaj.org-article:8f22b09d04fc440a8e18277bbdbd61a02021-12-02T17:15:33ZGene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma10.1038/s41598-021-88253-02045-2322https://doaj.org/article/8f22b09d04fc440a8e18277bbdbd61a02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88253-0https://doaj.org/toc/2045-2322Abstract Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein–protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.Om KulkarniPierre-Emmanuel SugierJulie GuibonAnne Boland-AugéChristine LonjouDelphine Bacq-DaianRobert OlasoCarole RubinoVincent SouchardFrédérique RachediJuan Jesus Lence-AntaRosa Maria OrtizConstance XhaardPierre Laurent-PuigClaire MulotAnne-Valérie GuizardClaire SchvartzMarie-Christine Boutron-RuaultEvgenia OstroumovaAusrele KesminieneJean-François DeleuzePascal GuénelFlorent De VathaireThérèse TruongFabienne LesueurNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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DOAJ |
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| topic |
Medicine R Science Q |
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Medicine R Science Q Om Kulkarni Pierre-Emmanuel Sugier Julie Guibon Anne Boland-Augé Christine Lonjou Delphine Bacq-Daian Robert Olaso Carole Rubino Vincent Souchard Frédérique Rachedi Juan Jesus Lence-Anta Rosa Maria Ortiz Constance Xhaard Pierre Laurent-Puig Claire Mulot Anne-Valérie Guizard Claire Schvartz Marie-Christine Boutron-Ruault Evgenia Ostroumova Ausrele Kesminiene Jean-François Deleuze Pascal Guénel Florent De Vathaire Thérèse Truong Fabienne Lesueur Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| description |
Abstract Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein–protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk. |
| format |
article |
| author |
Om Kulkarni Pierre-Emmanuel Sugier Julie Guibon Anne Boland-Augé Christine Lonjou Delphine Bacq-Daian Robert Olaso Carole Rubino Vincent Souchard Frédérique Rachedi Juan Jesus Lence-Anta Rosa Maria Ortiz Constance Xhaard Pierre Laurent-Puig Claire Mulot Anne-Valérie Guizard Claire Schvartz Marie-Christine Boutron-Ruault Evgenia Ostroumova Ausrele Kesminiene Jean-François Deleuze Pascal Guénel Florent De Vathaire Thérèse Truong Fabienne Lesueur |
| author_facet |
Om Kulkarni Pierre-Emmanuel Sugier Julie Guibon Anne Boland-Augé Christine Lonjou Delphine Bacq-Daian Robert Olaso Carole Rubino Vincent Souchard Frédérique Rachedi Juan Jesus Lence-Anta Rosa Maria Ortiz Constance Xhaard Pierre Laurent-Puig Claire Mulot Anne-Valérie Guizard Claire Schvartz Marie-Christine Boutron-Ruault Evgenia Ostroumova Ausrele Kesminiene Jean-François Deleuze Pascal Guénel Florent De Vathaire Thérèse Truong Fabienne Lesueur |
| author_sort |
Om Kulkarni |
| title |
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| title_short |
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| title_full |
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| title_fullStr |
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| title_full_unstemmed |
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| title_sort |
gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/8f22b09d04fc440a8e18277bbdbd61a0 |
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