Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure

Abstract

Background Gene environmental interaction analysis can identify novel genetic factors for blood pressure. We performed genome-wide analyses to identify genomic loci that interact with potassium to influence blood pressure (BP) using single marker (one and two degrees of freedom [DF] joint tests) and gene-based tests among Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Methods and Results Among 1,876 GenSalt participants, the average of three urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero-sphygmomanometer. A total of 2.2 million SNPs 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). SNP and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The one 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 two 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 the 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. 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 SNP- and gene-based interactions with potassium.

Advances in Genomics Research of Blood Pressure Responses to Dietary Sodium and Potassium Intakes

“…55 Additional loci identified in the GenSalt GWAS of blood pressure during potassium intervention include variants at ARL4C , which was reported to be involved in lipid metabolism and inflammation, and SALL1 , which has previously been identified for blood pressure–related traits, including C-reactive protein and kidney function. 74 Genes identified in genome-wide gene by potassium interaction analyses include ARL15 and RANBP3L , which have been shown to be involved in regulating adipocyte and mesenchymal stem cell differentiation, respectively. 75,76 In total, findings of genetic research for potassium sensitivity have provided interesting insights into potential mechanisms underlying hypertension.…”