The replication of genome-wide significant association signals in independent populations is a practical approach for characterizing gene-disease relationships. Therefore, we sought to explore the top 10 polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians. This was a hospital-based study involving 1009 patients with essential hypertension and 756 normotensive controls from Qiqihar city, China. Genotyping was conducted with a polymerase chain reaction-ligase detection reaction method. All polymorphisms except for rs6825911 satisfied Hardy-Weinberg equilibrium. Overall, the genotype differences between the patients and controls were significant for rs35444 (P < 0.001), rs11191548 (P = 0.017) and rs17249754 (P = 0.017). The per-minor-allele odds ratios of rs35444, rs11191548 and rs17249754 were 0.54 (95% confidence interval (95% CI): 0.46-0.62; P < 0.01), 1.23 (95% CI: 1.07-1.43; P = 0.005) and 1.23 (95% CI: 1.07-1.41; P = 0.004), respectively. Similarly, the carriers of minor homozygotes had a significant reduction in adjusted systolic and diastolic blood pressure for rs35444 (P < 0.01) but an increase for both rs11191548 (P < 0.01) and rs17249754 (P < 0.04). Further application of the genetic risk score method indicated that subjects with risk scores of 8, 10 and 12-16 had 1.66-fold (95% CI: 1.01-2.72), 1.72-fold (95% CI: 1.03-2.86) and 1.97-fold (95% CI: 1.12-3.46) increases, respectively, in the odds of developing hypertension, and similar increases were also observed for blood pressure. Taken together, our findings demonstrate that although only three of the top 10 polymorphisms were successfully validated in the northeastern Han Chinese population, the genetic risk score analyses led us to more profound insights into the possible joint effects of multiple polymorphisms on hypertension risk and blood pressure variation.