title: Replication of the top 10 most significant polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians.
abstract: 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.
authors.affiliation: Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Changzhu
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Property Theory and Complication, Science of Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: 1] Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [3] State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: 1] Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
mesh_terms: D000368:Aged; D044466:Asian People; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012959:Socioeconomic Factors
chemical_list: D004247:DNA