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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

ABSTRACT: We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm?Hg for mean arterial pressure and from 0.03 to 0.21 mm?Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

SUBMITTER: Kelly TN

PROVIDER: S-EPMC3972802 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

Kelly Tanika N TN Takeuchi Fumihiko F Tabara Yasuharu Y Edwards Todd L TL Kim Young Jin YJ Chen Peng P Li Huaixing H Wu Ying Y Yang Chi-Fan CF Zhang Yonghong Y Gu Dongfeng D Katsuya Tomohiro T Ohkubo Takayoshi T Gao Yu-Tang YT Go Min Jin MJ Teo Yik Ying YY Lu Ling L Lee Nanette R NR Chang Li-Ching LC Peng Hao H Zhao Qi Q Nakashima Eitaro E Kita Yoshikuni Y Shu Xiao-Ou XO Kim Nam Hee NH Tai E Shyong ES Wang Yiqin Y Adair Linda S LS Chen Chien-Hsiun CH Zhang Shihiu S Li Changwei C Nabika Toru T Umemura Satoshi S Cai Qiuyin Q Cho Yoon Shin YS Wong Tien Yin TY Zhu Jingwen J Wu Jer-Yuarn JY Gao Xin X Hixson James E JE Cai Hui H Lee Juyoung J Cheng Ching-Yu CY Rao Dabeeru C DC Xiang Yong-Bing YB Cho Myeong-Chan MC Han Bok-Ghee BG Wang Aili A Tsai Fuu-Jen FJ Mohlke Karen K Lin Xu X Ikram Mohammad Kamran MK Lee Jong-Young JY Zheng Wei W Tetsuro Miki M Kato Norihiro N He Jiang J

Hypertension (Dallas, Tex. : 1979) 20130903 5

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replicati ...[more]

PMID: 24001895

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Project description:BackgroundPulse pressure (PP) and mean arterial pressure (MAP) are well-established markers of cardiovascular risk. In this study, we aimed to assess the temporal trend and associated factors of PP and MAP in Chinese children and adolescents.MethodsFrom the China Health and Nutrition Survey 1991-2015, a total of 11,123 children and adolescents aged 7-17 years were included. Stratified analyses and generalized estimating equation (GEE) were conducted to compare the trends of PP and MAP by age and sex over two decades, along with the calculation of average relative increase (ARI). Moreover, multivariable linear regression was used to estimate the associated factors of PP and MAP.ResultsDuring 1991-2015, upward trends were observed in both PP and MAP levels, with ARI of 0.30 and 0.34%, respectively. PP was higher in boys [PP1991 33.9 mmHg (95%CI, 33.40-34.33) to PP2015 35.4 mmHg (34.74-36.15)] than in girls [PP1991 33.3 mmHg (32.83-33.72) to PP2015 34.3 mmHg (33.59-34.99)]. PP was also higher in participants aged 13-17 years [PP1991 36.1 mmHg (35.63-36.62) to PP2015 38.3 mmHg (37.35-39.21)] than in those aged 7-12 years [PP1991 31.5 mmHg (31.09-31.88) to PP2015 33.7 mmHg (33.16-34.30)]. Similar results were found in MAP. Participants with high economic status, general obesity and central obesity, were more likely to have wider PP (β higheconomicstatus = 0.60, 95% CI, 0.19-1.02; β generalobesity = 1.38, 0.87-1.89; β centralobesity = 1.34, 0.70-1.97; all P-values < 0.001) and higher MAP (β higheconomicstatus = 0.82, 0.38-1.26; β generalobesity = 2.88, 2.33-3.42; β centralobesity = 3.14, 2.47-3.80; all P-values < 0.001). Body mass index (BMI) and waist circumference (WC) were positively correlated with PP (β BMI = 0.18, 0.13-0.24; β WC = 0.10, 0.08-0.12; both P-values < 0.001) and MAP (β BMI = 0.43, 0.37-0.49; β WC = 0.20, 0.18-0.22; both P-values < 0.001). In addition, rural setting and glucose level were positively associated with PP (both P < 0.05), while north region residency, uric acid, and total cholesterol were found to be positively associated with MAP (all P < 0.05).ConclusionPP and MAP levels have been increasing dramatically in Chinese children and adolescents over the last two decades. Age, sex, economic status, geographic factors, anthropometric and cardiometabolic factor were positively associated with PP and MAP in pediatric population.

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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

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