Abstract
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.
Highlights
High blood pressure is the heritable risk factor for cardiovascular and kidney diseases
In the analysis of world data, one in three adults is expected to be affected by high blood pressure up to 2025, while macro or microvascular complications are not limited to extreme ranges of systolic and diastolic blood pressures (SBP and Diastolic Blood Pressure (DBP))[3]
In an inquiry of GWAS summary data on blood pressure related phenotypes in UK Biobank and Japanese population, we found out similar associations of detected variants on ZBED9 with DBP (P value ≤ 5 × 10–8) and HTN (P value ≤ 1 × 10–4) in UK Biobank, while the associations were not significant in Japanese population (Table 3)
Summary
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. 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 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. Risky or preventive genetic variants after adjusting for environmental risk factors Promising results from these hypothesis-free studies addressing different pathophysiologic pathways and gene targets for future pharmacologic interventions in complex d iseases[8]
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