Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study

Changwei Li, Jiang He, Jing Chen, Jinying Zhao, Dongfeng Gu, James E. Hixson, Dabeeru C. Rao, Cashell E. Jaquish, Charles C. Gu, Jichun Chen, Jianfeng Huang, Shufeng Chen, Tanika N. Kelly

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18 Scopus citations

Abstract

We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 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 Multi-Ethnic Study of Atherosclerosis (MESA). 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 UST rs13211840 on diastolic BP (P=3.13×10-9). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10-12) and LOC105369882 rs11104632 (P=4.51×10-8) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10-22) and mean arterial pressure (P=2.86×10-15). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10-7), C2orf80 (P<1.00×10-12), EPHA6 (P=2.88×10-7), SCOC-AS1 (P=4.35×10-14), SCOC (P=6.46×10-11), CLGN (P=3.68×10-13), MGAT4D (P=4.73×10-11), ARHGAP42 (P≤1.00×10-12), CASP4 (P=1.31×10-8), and LINC01478 (P=6.75×10-10) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium.

Original languageEnglish
Pages (from-to)348-355
Number of pages8
JournalHypertension
Volume68
Issue number2
DOIs
StatePublished - Aug 1 2016

Keywords

  • blood pressure
  • genes
  • genome-wide association study
  • sodium

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    Li, C., He, J., Chen, J., Zhao, J., Gu, D., Hixson, J. E., Rao, D. C., Jaquish, C. E., Gu, C. C., Chen, J., Huang, J., Chen, S., & Kelly, T. N. (2016). Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study. Hypertension, 68(2), 348-355. https://doi.org/10.1161/HYPERTENSIONAHA.115.06765