A Two-Stage Whole-Genome Gene Expression Association Study of Young-Onset Hypertension in Han Chinese Population of Taiwan

Abstract Hypertension is an important public health problem in the world. Since the intermediate position of the gene expression between genotype and phenotype makes it suitable to link genotype to phenotype, we carried out a two-stage whole-genome gene expression association study to find differentially expressed genes and pathways for hypertension. In the first stage, 126 cases and 149 controls were used to find out the differentially expressed genes. In the second stage, an independent set of samples (127 cases and 150 controls) was used to validate the results. Additionally, we conducted a gene set enrichment analysis (GSEA) to search for differentially affected pathways. A total of nine genes were implicated in the first stage (Bonferroni-corrected p-value < 0.05). Among these genes, ZRANB1, FAM110A, PREP, ANKRD9 and LAMB2 were also differentially expressed in an existing database of hypertensive mouse model (GSE19817). A total of 16 pathways were identified by the GSEA. ZRANB1 and six pathways identified are related to TNF-α. Three pathways are related to interleukin, one to metabolic syndrome, and one to Hedgehog signaling. Identification of these genes and pathways suggest the importance of 1. inflammation, 2. visceral fat metabolism, and 3. adipocytes and osteocytes homeostasis in hypertension mechanisms and complications