Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).

Changwei Li, Jiang He, Jing Chen, Jinying Zhao, Dongfeng Gu, James E Hixson, Dabeeru C Rao, Cashell E Jaquish, Treva K Rice, Yun Ju Sung, Tanika N Kelly
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Abstract

Background: Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity).

Methods and results: Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10-4) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for ARL15 rs16882447 on systolic BP (P=2.83×10-9) and RANBP3L rs958929 on pulse pressure (P=1.58×10-8). The 2 df tests confirmed the ARL15 rs16882447 signal for systolic BP (P=1.15×10-9). Genome-wide gene-based analysis identified CC2D2A (P=2.59×10-7) at 4p15.32 and BNC2 (P=4.49×10-10) at 9p22.2 for systolic BP, GGNBP1 (P=1.18×10-8), and LINC00336 (P=1.36×10-8) at 6p21 for diastolic BP, DAB1 (P=1.05×10-13) at 1p32.2, and MIR4466 (P=5.34×10-8) at 6q25.3 for pulse pressure. The BNC2 (P=3.57×10-8) gene was also significant for mean arterial pressure.

Conclusions: We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.

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关于血压的全基因组基因-钾相互作用分析:GenSalt 研究(盐敏感性遗传流行病学网络)。
背景:基因-环境交互作用分析可确定血压(BP)的新遗传因素。我们在盐敏感性遗传流行病学网络(Genetic Epidemiology Network of Salt Sensitivity)研究的中国参与者中进行了全基因组分析,利用单标记(1 和 2 df 联合检验)和基于基因的检验来确定与钾相互作用影响血压的基因组位点:在 1876 名 GenSalt 参与者中,采用 3 次尿样的平均值来估算钾的排泄量。使用随机零点血压计测量了 9 次血压。使用 Affymetrix 6.0 基因型数据和中国北京汉族和日本东京 HapMap 参考面板对总共 220 万个单核苷酸多态性进行了估算。在 775 名参加 MESA(多种族动脉粥样硬化研究)的中国人中,对 GenSalt 的有希望的发现(P-4)进行了评估,以进行复制。对 GenSalt 和 MESA 研究的单核苷酸多态性和基于基因的结果进行了元分析,以确定全基因组的重要性。1 df 检验确定了 ARL15 rs16882447 与收缩压的相互作用(P=2.83×10-9)和 RANBP3L rs958929 与脉压的相互作用(P=1.58×10-8)。2 df 检验证实了 ARL15 rs16882447 信号对收缩压的影响(P=1.15×10-9)。基于全基因组的基因分析发现,4p15.32 的 CC2D2A(P=2.59×10-7)和 9p22.2 的 BNC2(P=4.49×10-10)与收缩压有关,GGNBP1(P=1.18×10-8)、6p21处的LINC00336(P=1.36×10-8)与舒张压有关,1p32.2处的DAB1(P=1.05×10-13)和6q25.3处的MIR4466(P=5.34×10-8)与脉压有关。BNC2(P=3.57×10-8)基因对平均动脉压也有显著影响:通过研究单核苷酸多态性和基因与钾的相互作用,我们发现了 2 个新的血压基因位点和 6 个基因。
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Circulation: Cardiovascular Genetics
Circulation: Cardiovascular Genetics CARDIAC & CARDIOVASCULAR SYSTEMS-GENETICS & HEREDITY
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6-12 weeks
期刊介绍: Circulation: Genomic and Precision Medicine considers all types of original research articles, including studies conducted in human subjects, laboratory animals, in vitro, and in silico. Articles may include investigations of: clinical genetics as applied to the diagnosis and management of monogenic or oligogenic cardiovascular disorders; the molecular basis of complex cardiovascular disorders, including genome-wide association studies, exome and genome sequencing-based association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned approaches, including phenome-wide association studies, or with environmental or lifestyle factors; pharmacogenomics; regulation of gene expression; gene therapy and therapeutic genomic editing; systems biology approaches to the diagnosis and management of cardiovascular disorders; novel methods to perform any of the aforementioned studies; and novel applications of precision medicine. Above all, we seek studies with relevance to human cardiovascular biology and disease.
期刊最新文献
Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis. Genetic Testing in Pediatric Left Ventricular Noncompaction. Novel Mutation in FLNC (Filamin C) Causes Familial Restrictive Cardiomyopathy. FLNC (Filamin-C): A New(er) Player in the Field of Genetic Cardiomyopathies.
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