학술논문
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma
Document Type
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
Source
Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
Subject
Language
English
ISSN
2045-2322
Abstract
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