Genome-Wide Approach of Gene-Nutrient Intake Interaction Study for Essential Hypertension in a Large Korean Cohort (KoGES)

Background/Objectives: There is limited evidence on gene-nutrient interaction associated with hypertension (HTN). We examined interactions between genotypes and various nutrients that influenced high blood pressure (BP). Methods: Data were obtained from a total of 50,808 participants from the Korean Genome and Epidemiology Study (KoGES). Dietary intake was assessed by a food frequency questionnaire, and dietary reference intakes (DRIs) were set. We performed genome-wide association analyses (GWAS) and subsequent interaction analyses with genome-wide significant SNPs to identify genomic loci that interact with specific nutrients associated with HTN. Results: We identified one locus near the CUB and Sushi Multiple Domains 1 (CSMD1) gene that showed interaction with dietary iron and vitamin B6 (Vit.B6) intake and significantly influenced HTN risk. Among the individuals consuming iron above DRI (9.5 mg/day for men, 9.25 mg/day for women), carriers of the rs13282715 minor allele (A) at 8p23.2 showed a lower risk of HTN than those who did not (odds ratio [OR] 0.723, 95% confidence interval [CI] (0.644-0.813), p-value 4.858 × 10^-8; interaction p-value 1.336 × 10^-3). Among the individuals consuming Vit.B6 above DRI (1.5 mg/day for men, 1.4 mg/day for women), carriers of the same variant rs13282715 minor allele (A) also showed a lower risk of HTN (OR 0.733, 95% CI 0.733 (0.656-0.819), p-value 4.121 × 10^-8; interaction p-value 7.183 × 10^-4). Conclusions: We identified a novel gene-nutrient interaction regarding dietary iron and Vit.B6 intake affecting the risk of HTN in Korean adults. This suggests individuals with the variant may benefit from lower HTN risk from dietary intervention of iron and Vit.B6 intake. Further studies with larger diverse populations are warranted to validate our findings.