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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Article numbere001811
JournalCirculation: Cardiovascular Genetics
Issue number6
StatePublished - Dec 1 2017


  • blood pressure
  • genome-wide association study
  • genotype
  • potassium


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