Abstract P348: Validation of SGCD (rs2116737) Genotype-Discrimination Interaction as a Determinant of Blood Pressure Variation in the Jackson Heart Study

Abstract

Introduction: Previous anthropological studies have demonstrated the utility of integrating genetic and psychosocial data, such as discrimination, to understand complex phenotypes such as blood pressure (BP). In these studies, including both single nucleotide polymorphisms (SNP) and psychosocial measures in the model only revealed significant SNPs after accounting for gene by social environment interactions. Methods: We sought to externally validate SNPs associated with BP in African Americans (AAs) identified in a study by Quinlan et al. in 2016 that incorporated novel measures of unfair treatment/discrimination and revealed new genes and biological pathways relevant to BP variation. Our validation was done using a larger cohort study of AAs, the Jackson Heart Study (JHS). Systolic and diastolic BP were measured twice in the same visit using a random-zero mercury sphygmomanometer and averaged. During this visit, perceived discrimination was assessed as lifetime occurrence of unfair treatment in nine social domains using the JHS discrimination instrument. Using available GWAS data, 28 significant SNPs were imputed from 1000 Genomes Project Phase 1 (version 3). Our analysis was conducted separately on participants who reported use of BP medications (n= 1532) and those who did not (n=1407). We similarly tested for associations of SNPs with BP using 3 linear regression models adjusting for global ancestry, sex, age, education, BMI, and relatedness. Model 1 tested only the SNPs, model 2 tested the SNPs and discrimination, and model 3 tested an interaction between SNPs and discrimination. Results: JHS participants were 62% female, with a mean age of 55 years, mean BMI of 32, mean systolic BP of 127 and mean diastolic BP of 76. Participants on average experienced unfair treatment in three domains in their lifetime. In participants not on BP medications, we found that rs2116737, in the gene SGCD , achieved Bonferroni-corrected significance (p < 0.004) with systolic BP in a recessive genotype model (β= 11.92; p =2.00х10 -4 ) and was only identified through model 3, the gene-discrimination interaction model. No significant findings were seen in patients using BP medications. Conclusions: rs2116737 was validated in the JHS for a gene-discrimination interaction. rs2116737 is an intronic variant in SGCD , a gene that is highly expressed in arterial tissue, suggesting vascular regulation as a possible mechanism behind the interaction. In conclusion, the findings suggest accounting for a gene by social environment interaction can identify new SNPs that deserve further investigation in understanding BP variation.