Hemerich Daiane, van Setten Jessica, Tragante Vinicius, Asselbergs Folkert W
Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands.
CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
Front Cardiovasc Med. 2018 Apr 4;5:25. doi: 10.3389/fcvm.2018.00025. eCollection 2018.
High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions. Phenotypic cell-type specificity analyses and expression quantitative trait loci show predominant vascular and cardiac tissue involvement for blood pressure-associated variants. Maps of chromosomal conformation and expression quantitative trait loci (eQTL) in critical tissues identified 2,424 genes interacting with blood pressure-associated loci, of which 517 are druggable. Integrating genome, regulome and transcriptome information in relevant cell-types could help to functionally annotate blood pressure associated loci and identify drug targets.
高血压是多种心血管疾病公认的风险因素。全基因组关联研究已成功发现900多个与血压相关的基因座。然而,这些基因座导致疾病的机制仍相对不明,因为与高血压相关的变异中只有不到10%位于编码区。表型细胞类型特异性分析和表达数量性状基因座显示,与血压相关的变异主要涉及血管和心脏组织。关键组织中的染色体构象图谱和表达数量性状基因座(eQTL)确定了2424个与血压相关基因座相互作用的基因,其中517个是可成药的。整合相关细胞类型中的基因组、调控组和转录组信息,有助于对血压相关基因座进行功能注释并识别药物靶点。