A pilot genome-wide association study of ischemic heart disease with co-occurring arterial hypertension in a Kazakh cohort

Abstract

Genome-wide association studies (GWAS) of ischemic heart disease (IHD) remain underrepresented in Central Asian populations. We conducted a pilot GWAS of ischemic heart disease with co-occurring arterial hypertension (IHD-HTN) in an ethnic Kazakh cohort to identify candidate loci for future replication. This study included 470 Kazakh individuals, comprising of 240 cases and 230 controls genotyped using the Illumina Infinium Global Screening Array-24 v 3.0. Association testing was performed using logistic regression under an additive genetic model adjusted for age, sex, and the first 10 principal components. Post-imputation GWAS was performed using high-quality imputed variants. Secondary analyses included MAGMA and KGWAS prioritization. In the array-based GWAS, no variant reached the Bonferroni-corrected significance threshold (P < 1.53 × 10 −7 ). The strongest SNP association was observed for rs1511924 at chromosome 16 mapped to the ZFHX3 gene (OR = 0.49, 95% CI = 0.37–0.66; P = 1.00 × 10 −6 ). Post-imputation GWAS supported the same locus with rs12598508 (P = 4.93 × 10 −7 ) and rs1511924 (P = 5.15 × 10 −7 ) among the strongest signals, although neither reached the genome-wide significance. Secondary MAGMA and KGWAS analyses did not provide stable evidence for additional loci. To our knowledge, this is the first pilot GWAS focused on IHD with co-occurring arterial hypertension in a Kazakh cohort. Although no Bonferroni-significant SNP associations were identified, the ZFHX3 region emerged as the strongest suggestive candidate locus and requires independent replication. Larger Central Asian cohorts and population-specific reference resources are required to validate these findings.