Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension

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.

The AGT epistasis pattern proposed a novel role for ZBED9 in regulating blood pressure: Tehran Cardiometabolic genetic study (TCGS)

“…Similar to GWAS ndings in the European population, AGT and TNXB with a consistent effect on SBP, DBP and HTN are contributed to blood pressure regulation among Iranian families (9). Further, a recent genome-wide association study in the Iranian population discovered a new locus (ZBED9) for hypertension that was con rmed in a linkage analysis on different sets of blood pressure traits and replicated in summary statistics of UK Biobank on DBP and HTN (10).…”

“…TLGS is a population-based cohort started in 1999, and study subjects have been followed up through six phases (every three years) on non-communicable disorders' (NCDs) and related risk factors (14). The current study extracted 4,214 unrelated participants aged 18 or above, based on the well-designed protocol in previous GWAS in TCGS (9,10). HTN incident cases and a random sample of healthy individuals with two or more follow-up records were included in the study using a nested case-control sampling design.…”

“…Blood samples of TCGS participants were genotyped using humanOmniExpress-24-v1 bead chips on 652919 single nucleotide polymorphisms with an average mean distance of 4 kilobases for each individual at deCODE genetic company (16). Genomic quality control (QC) was implemented in comprehensive steps (10,17).…”

SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study

“…Studies have shown that most cases of hypertension are affected by environmental and disease factors, including drinking, smoking, changes in daily habits, hyperlipidemia, atherosclerosis, and diabetes. At the same time, genetic association studies have shown that genetic susceptibility has a great influence on the risk and prognosis of hypertension Kolifarhood et al [ 5 ]. However, the genetic factors affecting hypertension are too complicated.…”

A CNN deep learning model to improve SNP-based hypertension risk prediction accuracy

“…In phase two or three, genome samples from white blood cells were genotyped by standard proteinase K method extracted with HumanOmniExpress-24-v1-0 chip by deCODE according to Illumina device (30). Genomic data for each individual has 600K SNPs stored in the ped le.…”