A regulatory SNP in AKAP13 is associated with blood pressure in Koreans.

High blood pressure contributes to more than 10 million deaths per year worldwide through stroke and ischemic heart disease. Yet, genome-wide association studies (GWASs) have identified a small fraction of its underlying genetic factors. To identify biologically important single-nucleotide polymorphisms (SNPs) that regulate variations in blood pressure, we analyzed SNPs in a genome-wide association study. Genome-wide genotype data (original study n = 7551, SNP = 352,228; replication study n = 3703, SNP = 20) were obtained from the Korea National Institute of Health, wherein 29,921 of 352,228 SNPs lay within 5 kbp upstream of genes. Linear regression analysis was performed for systolic and diastolic blood pressure (DBP) by controlling for cohort, age, sex and body mass index. For the 20 SNPs that were associated with both blood pressure values, a replication study was performed in an independent population. A total of 20 SNPs were significantly associated with both blood pressure values in the original study, 13 of which lay in a conserved transcription factor-binding site. One SNP (rs11638762), in the GATA-3 binding site upstream of the AKAP13 gene, was significantly replicated in another cohort (P-value of the meta-analysis = 1.4 × 10(-5) for systolic blood pressure and 6.3 × 10(-4) for DBP). A functional GWAS was performed using upstream SNPs, and a novel genetic factor (AKAP13), which is essential for cardiac myocyte development in mice, was identified as a regulator of blood pressure.