Abstract 54: Genome-Wide Association Analysis of Gene-Sodium Interactions on Blood Pressure Phenotypes: The GenSalt Study
Background: Elevated blood pressure (BP) is a major public health challenge. Although the heritability of BP has been long established, current findings can explain only a small proportion of the BP variability attributed to genetic factors. Recent studies indicate that gene-environmental interactions may help to identify novel BP loci. Hence, the current study aimed to identify genetic variants influencing BP regulation by conducting genome-wide gene-sodium interaction analyses among 1,906 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 sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 868,158 autosomal single nucleotide polymorphisms (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 SNP-sodium interactions on BP, adjusting for age, gender, and body mass index. Promising findings (interaction term P <1.00х10-6) from GenSalt were further evaluated for replication among Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with available data from the database of genotypes and phenotypes (dbGaP). SNP effects in GenSalt and MESA were meta-analyzed using inverse-variance weighted fixed effect models.
Results: The meta-analyses identified 3 novel loci that significantly interacted with sodium to influence BP phenotypes. SNP-sodium interactions on systolic BP were identified for NEK2 variant rs10494938 at 1q32.3 (GenSalt P=2.19х10-6, MESA P=4.35х10-4, and Meta-analysis P= 3.93х10-8). In addition, CASP4 variant rs1944900 at 11q22.3 interacted with sodium to influence both systolic BP (GenSalt P=1.24х10-9, MESA P=4.22х10-2, and Meta-analysis P= 1.14х10-10) and mean arterial pressure (GenSalt P=1.68х10-9, MESA P=4.27х10-2, and Meta-analysis P= 1.91х10-10). Furthermore, C9orf3 variant rs17679141 at 9q22.32 interacted with sodium to influence diastolic BP (GenSalt P=2.85х10-8, MESA P=4.55х10-2, and Meta-analysis P=4.61х10-9). The 3 variants all physically mapped to the intronic regions of their corresponding genes.
Conclusion: The current study identified 3 novel loci which may interact with dietary sodium intake to influence BP phenotypes.
Author Disclosures: C. Li: None. J. He: None. J. Hixson: None. D. Gu: None. D. Rao: None. L. Shimmin: None. J. Huang: None. C. Gu: None. J. Chen: None. J. Li: None. C. Jaquish: None. T.N. Kelly: None.
- © 2015 by American Heart Association, Inc.