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Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

ABSTRACT: BACKGROUND:Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. METHODS AND RESULTS:We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ?46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10-8 and 2.5×10-6, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P=5.03×10-8, stage-2 P=8.64×10-3, joint P=2.63×10-8) and mean arterial pressure (stage-1 P=3.59×10-9, stage-2 P=2.35×10-2, joint P=2.64×10-8). Three previously reported BP loci (WBP1L, NT5C2, and ATP2B1) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P=8.55×10-6, stage-2 P=1.62×10-5, joint P=3.28×10-9) and mean arterial pressure (stage-1 P=9.19×10-7, stage-2 P=9.69×10-5, joint P=2.15×10-9) phenotypes. Fourteen genes (TMEM180, ACTR1A, SUFU, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, C10orf32-ASMT, AS3MT, CNNM2, and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (P=1.27×10-4 and 3.30×10-4, respectively). CONCLUSIONS:We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.

SUBMITTER: Li C

PROVIDER: S-EPMC5704911 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

Li Changwei C Kim Yun Kyoung YK Dorajoo Rajkumar R Li Huaixing H Lee I-Te IT Cheng Ching-Yu CY He Meian M Sheu Wayne H-H WH Guo Xiuqing X Ganesh Santhi K SK He Jiang J Lee Juyoung J Liu Jianjun J Hu Yao Y Rao Dabeeru C DC Tsai Fuu-Jen FJ Koh Jia Yu JY Hu Hua H Liang Kae-Woei KW Palmas Walter W Hixson James E JE Han Sohee S Teo Yik-Ying YY Wang Yiqin Y Chen Jing J Lu Chieh Hsiang CH Zheng Yingfeng Y Gui Lixuan L Lee Wen-Jane WJ Yao Jie J Gu Dongfeng D Han Bok-Ghee BG Sim Xueling X Sun Liang L Zhao Jinying J Chen Chien-Hsiun CH Kumari Neelam N He Yunfeng Y Taylor Kent D KD Raffel Leslie J LJ Moon Sanghoon S Rotter Jerome I JI Ida Chen Yii-der YD Wu Tangchun T Wong Tien Yin TY Wu Jer-Yuarn JY Lin Xu X Tai E-Shyong ES Kim Bong-Jo BJ Kelly Tanika N TN

Circulation. Cardiovascular genetics 20170401 2

<h4>Background</h4>Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP.<h4>Methods and results</h4>We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a <i>P</i><5.0×10<sup>-8</sup> and 2.5×10<sup>-</sup><sup>6</sup>, ...[more]

PMID: 28348047

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Project description:ObjectiveTo evaluate and quantify the future risk of cardiovascular events in young adults with high blood pressure.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and Web of Science were searched from inception to 6 March 2020. Relative risks were pooled using a random effects model and expressed with 95% confidence intervals. Absolute risk difference was calculated. Dose-response relations between blood pressure and individual outcomes were assessed by a restricted cubic spline model.Eligibility criteria for selecting studiesStudies were selected that investigated the adverse outcomes of adults aged 18-45 with raised blood pressure. The primary study outcome was a composite of total cardiovascular events. Coronary heart disease, stroke, and all cause mortality were examined as secondary outcomes.ResultsSeventeen observational cohorts consisting of approximately 4.5 million young adults were included in the analysis. The average follow-up was 14.7 years. Young adults with normal blood pressure had increased risk of cardiovascular events compared with those with optimal blood pressure (relative risk 1.19, 95% confidence interval 1.08 to 1.31; risk difference 0.37, 95% confidence interval 0.16 to 0.61 per 1000 person years). A graded, progressive association was found between blood pressure categories and increased risk of cardiovascular events (high normal blood pressure: relative risk 1.35, 95% confidence interval 1.22 to 1.49; risk difference 0.69, 95% confidence interval 0.43 to 0.97 per 1000 person years; grade 1 hypertension: 1.92, 1.68 to 2.19; 1.81, 1.34 to 2.34; grade 2 hypertension: 3.15, 2.31 to 4.29; 4.24, 2.58 to 6.48). Similar results were observed for coronary heart disease and stroke. Generally, the population attributable fraction for cardiovascular events associated with raised blood pressure was 23.8% (95% confidence interval 17.9% to 28.8%). The number needed to treat for one year to prevent one cardiovascular event was estimated at 2672 (95% confidence interval 1639 to 6250) for participants with normal blood pressure, 1450 (1031 to 2326) for those with high normal blood pressure, 552 (427 to 746) for those with grade 1 hypertension, and 236 (154 to 388) for those with grade 2 hypertension.ConclusionsYoung adults with raised blood pressure might have a slightly increased risk of cardiovascular events in later life. Because the evidence for blood pressure lowering is limited, active interventions should be cautious and warrant further investigation.

Project description:BackgroundBlood pressure variability (BPV) is an important risk factor for cardiovascular events in hemodialysis patients. We sought to determine the impact of BPV on hemodialysis access thrombosis.MethodsWe enrolled 1,011 prevalent hemodialysis patients from 12 hemodialysis centers since January 2018 and followed them until December 2020. Predialysis blood pressure (BP) was assessed at 12-week intervals. The coefficient of variation derived from 36 consecutive BP measurements was used as the metric for variability. The primary outcome was incident hemodialysis access thrombosis. Linear regression models were used to assess factors associated with BPV at baseline. Kaplan-Meier curves of the time until vascular access events were drawn and log-rank tests were calculated. Cox proportional hazards models were performed to assess the association of BPV with incident vascular access events.ResultsThe average coefficient of variance for systolic BPV was 10.9%. BPV was associated with age, body mass index, mean BP, diabetes, coronary and peripheral artery disease, history of access dysfunction, graft access, intradialytic hypotension, and use of antihypertensive medications. There were 194 access thrombosis events and 451 access stenosis events during a median follow-up period of 30 months. After adjustment of potential confounding factors, BPV was associated with increased risk of access thrombosis [hazard ratio = 1.27, 95% confidence interval (CI), 1.18-1.44, per 1 standard deviation increase in BPV]. The patients in the highest BPV quartile had 2.45 times the risk of thrombosis (CI, 1.62-3.70). The association was independent of average BP, intradialytic hypotension, and comorbidities. Similar trends of association were found in the subgroups analyzed. Comparative analysis using a time-varying variable model and different metrics of BPV showed consistent results.ConclusionOur findings underscored the impact of BP fluctuation on vascular access thrombosis.

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Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

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Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

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