GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE103nnn/GSE103305/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103305GEOGSEfalseThyroid State Regulates Gene Expression in Human Whole Blood CellsContext: Despite the well-recognized clinical features due to insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of TRα-expressing cells. Methods: We performed next-generation RNA sequencing on whole blood samples from 8 athyroid patients (4 females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene co-expression network analysis (WGCNA) was applied to identify thyroid state-related networks. Results: We detected 486 differentially expressed (DE) genes (fold-change above 1.5; multiple testing corrected P-value <0.05), of which 76 % were positively and 24 % were negatively regulated. Gene ontology (GO) enrichment analysis revealed that 3 biological processes were significantly overrepresented of which the process translational elongation showed the highest fold enrichment (7.3 fold, P=1.8 x 10-6). Comparative transcriptome analysis revealed significant overlap with DE-genes in muscle samples upon different thyroid state (1.7-fold enrichment; P=0.02). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO-analysis suggested that thyroid state regulates platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRα-expressing leukocytes. In addition, TH may regulate gene expression in platelets. Whole blood samples might potentially be used as a proxy for other TRα-expressing tissues in humans.2017/10/30GSE103305GSM2760050GSM2760053GSM2760054GSM2760051GSM2760052GSM2760057GSM2760046GSM2760058GSM2760047GSM2760055GSM2760044GSM2760045GSM2760056GSM2760048GSM2760059GSM276004916791SRP127016103305Homo sapiens[29069456]