Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2021 Jun 3;11(1):11699. doi: 10.1038/s41598-021-90925-w.
High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.
高血压是心血管疾病和肾脏疾病的遗传风险因素。血压特征的全基因组关联研究（GWAS）增加了我们对其潜在遗传基础的理解。然而，很大一部分 GWAS 是在欧洲人群中进行的，一些障碍使其他人群无法从他们的研究结果中受益。伊朗人群具有高度的基因组特异性，但迄今为止尚未在国际数据库中得到代表，因此为了填补这一空白，我们在 7694 名年龄在 18 岁及以上的来自德黑兰心脏代谢遗传研究（TCGS）的伊朗成年人中，研究了 652,919 个基因组变异对收缩压（SBP）、舒张压（DBP）和高血压（HTN）的影响。我们在调整不同环境预测因子集后，在全基因组边缘阈值上发现了与 HTN 相关的 ZBED9 一致信号。此外，在 DBP 和 SBP 上分别检测到 ABHD17C 上的强信号和 FBN1 上的提示信号，而在不同的 GWA 分析中这些信号并不一致。我们在独立样本中的连锁分析中证实了 ZBED9 与所有 BP 特征的关联。我们在英国生物库 GWAS 汇总数据中发现，ZBED9 与 DBP（全基因组阈值）和 HTN（名义阈值）的遗传变异具有相似的效应方向和等位基因频率的显著关联。虽然没有强有力的证据支持 ZBED9 在血压调节中的作用，但它为高血压和其他心血管疾病的多效性效应提供了新的见解。
