Glucocorticoids Unmask Silent Non-Coding Genetic Risk Variants for Common Diseases [STARR-seq]. Glucocorticoids Unmask Silent Non-Coding Genetic Risk Variants for Common Diseases [STARR-seq]

30 B-lymphoblastoid cell lines (LCLs) with genome-wide genotype data were treated with hydrocortisone (GR agonist) and CORT108297 (GR modulator), followed by RNA-seq to identify PGx-eQTLs. We then integrated GR chromatin immunoprecipitation-sequencing (ChIP-seq) to characterize the epigenetic function of PGx-eQTLs that interfere with GR response elements. We also applied a high-throughput enhancer assay (STARR-seq) using PGx-eQTL loci DNA sequences to “scan” for drug-dependent SNPs. Overall design: STARR-seq of targeted loci before and after hydrocortisone (GR agonist) and CORT108297 (GR modulator) treatment

本数据集以30株携带全基因组基因型数据的B淋巴母细胞样细胞系（B-lymphoblastoid cell lines, LCLs）为研究模型。分别使用氢化可的松（糖皮质激素受体（Glucocorticoid Receptor, GR）激动剂）与CORT108297（GR调节剂）对细胞进行处理，随后通过RNA测序（RNA-seq）鉴定药物基因组学表达数量性状基因座（Pharmacogenomics Expression Quantitative Trait Loci, PGx-eQTLs）。
后续整合糖皮质激素受体染色质免疫共沉淀测序（ChIP-seq）数据，以解析可干扰糖皮质激素受体应答元件的PGx-eQTLs的表观遗传功能。本研究还针对PGx-eQTLs位点的DNA序列，采用高通量增强子检测（STARR-seq）开展筛选，以识别药物依赖性单核苷酸多态性位点（SNPs）。
整体实验设计：在施加氢化可的松（GR激动剂）与CORT108297（GR调节剂）处理前后，分别对靶向位点进行STARR-seq检测。