Abstract P253: Genomewide Gene-potassium Interaction Analyses on Blood Pressure: The GenSalt Study

Abstract

Background: The current study aimed to identify genes and variants influencing BP regulation by conducting genomewide single-marker and gene-based analyses of gene-potassium interactions among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Methods: GenSalt recruited 1,906 Chinese participants from 633 families. At baseline, one 24-hour and two 8-hour urine specimens were collected to measure urinary potassium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 868,158 autosomal SNPs were genotyped using Affymetrix Genomewide Human SNP array 6.0 (Affymetrix, Inc, Santa Clara, CA). Mixed effects models were used to test genome-wide 1 degree-of-freedom (df) SNP-potassium interactions and 2 df joint effects on BP, adjusting for age, gender, and body mass index. The GATES method was used to perform genome-wide gene-based analyses. Promising findings ( P <1.00х10 -4 ) from GenSalt were evaluated for replication among Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). SNP and gene effects were meta-analyzed across GenSalt and MESA studies. Results: The SNP based analyses identified 7 novel loci that significantly interacted with potassium to influence BP. The 1 df tests identified interactions for BNC variant rs16934920 on DBP (GenSalt P =1.07х10 -6 , MESA P =2.64х10 -3 , and Meta-analysis P = 2.31х10 -8 ) and MAP (GenSalt P =2.38х10 -8 , MESA P =2.08х10 -2 , and Meta-analysis P = 1.57х10 -9 ), and intergenic variant rs13210180 on PP (GenSalt P =2.43х10 -7 , MESA P =9.39х10 -3 , and Meta-analysis P = 4.24х10 -8 ). The 2 df joint tests additionally identified interactions for ANKMY1 variant rs6741340 (GenSalt P =4.43х10 -8 , MESA P =1.90х10 -2 , and Meta-analysis P = 1.04х10 -9 ) on SBP, intergenic variant rs2101828 on DBP (GenSalt P =6.96х10 -9 , MESA P =2.21х10 -2 , and Meta-analysis P = 6.52х10 -11 ) and MAP (GenSalt P =6.26х10 -11 , MESA P =1.20х10 -2 , and Meta-analysis P = 2.22х10 -13 ), and MTR variant rs10495384 (GenSalt P =1.44х10 -6 , MESA P =2.69х10 -2 , and Meta-analysis P = 3.11х10 -8 ), intergenic variants rs9815615 (GenSalt P =5.55х10 -7 , MESA P =1.00х10 -10 , and Meta-analysis P = 4.47х10 -19 ), and LINC00379 variant rs9583894 (GenSalt P =2.10х10 -8 , MESA P =4.31х10 -2 , and Meta-analysis P = 1.32х10 -9 ) on PP. Genomewide gene-based analysis of the 1 df and 2 df tests identified ACOT7 at 1p36.31, DAB1 at 1p32.2, PDK1 at 2q31.1, TRPM8 at 2q37.1, EGFEM1P at 3q26.2, EPHA6 at 3q11.2, CPEB2 at 4p15.33, FBXL17 at 5q21.3, RANBP3L at 5p13.2, ARID1B at 6q25.3, C6orf165 at 6q15, GGNBP1 at 6p21.31, BNC2 at 9p22.3, CUTC at 10q24.2, ARHGAP42 at 11q22.1, LINC00379 at 13q31.3, MTUS2 at 13q12.3, TMTC4 at 13q32.3, and SERPINA6 at 14q32.13 that were associated with at least one BP phenotype. Conclusion: The current study identified 7 novel loci and 19 genes which may interact with dietary potassium intake to influence BP phenotypes.