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
{"title":"Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).","authors":"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","doi":"10.1161/CIRCGENETICS.117.001811","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 <i>df</i> joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity).</p><p><strong>Methods and results: </strong>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 (<i>P</i><1.00×10<sup>-</sup><sup>4</sup>) 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 <i>df</i> tests identified interactions for <i>ARL15</i> rs16882447 on systolic BP (<i>P</i>=2.83×10<sup>-9</sup>) and <i>RANBP3L</i> rs958929 on pulse pressure (<i>P</i>=1.58×10<sup>-8</sup>). The 2 <i>df</i> tests confirmed the <i>ARL15</i> rs16882447 signal for systolic BP (<i>P</i>=1.15×10<sup>-9</sup>). Genome-wide gene-based analysis identified <i>CC2D2A</i> (<i>P</i>=2.59×10<sup>-7</sup>) at 4p15.32 and <i>BNC2</i> (<i>P</i>=4.49×10<sup>-</sup><sup>10</sup>) at 9p22.2 for systolic BP, <i>GGNBP1</i> (<i>P</i>=1.18×10<sup>-</sup><sup>8</sup>), and <i>LINC00336</i> (<i>P</i>=1.36×10<sup>-</sup><sup>8</sup>) at 6p21 for diastolic BP, <i>DAB1</i> (<i>P</i>=1.05×10<sup>-</sup><sup>13</sup>) at 1p32.2, and <i>MIR4466</i> (<i>P</i>=5.34×10<sup>-</sup><sup>8</sup>) at 6q25.3 for pulse pressure. The <i>BNC2</i> (<i>P</i>=3.57×10<sup>-</sup><sup>8</sup>) gene was also significant for mean arterial pressure.</p><p><strong>Conclusions: </strong>We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728702/pdf/nihms921927.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Cardiovascular Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1161/CIRCGENETICS.117.001811","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.
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.