Abstract 10651: Identification of Allele-Specific Gene Expression in Association with Blood Pressure

Abstract

Introduction: Risk of hypertension is explained by both behavioral and genetic factors that may act on transcriptomic mechanisms to affect blood pressure variability. Methods: Whole genome sequencing and RNA sequencing data were obtained on 1,671 Framingham Heart Study (FHS) participants (mean age 54±13 years). Allelic expression of heterozygous SNPs was measured and allelic imbalance was identified using a binomial test. SNPs with significant allelic imbalance were evaluated in linear regression to test the association between the reference/total allele count ratio and 1) systolic blood pressure (SBP), and 2) diastolic blood pressure (DBP). Models were adjusted for age, sex, BMI, and family structure. Results: At a Bonferroni-corrected p-value<6.4E-8, we identified 20,890 SNPs with significant allelic imbalance at MAF>0.01. Prior GWAS have identified >2,000 SNPs associated with SBP, DBP, or hypertension; we identified allelic expression imbalance of 60 SNPs (in 44 genes) that were reported in GWAS to be associated with SBP, and of eight SNPs (in two genes) that are associated with DBP. These genes were significantly enriched for the immune effector process pathway (p=1.4E-7). Fifteen SNPs were located in promoter or promoter-flanking regions, while the remaining SNPs were located in protein-coding regions. Seventeen SNPs were also cis -eQTLs, of which four transcripts also were associated with SBP or DBP in the FHS cohort. Conclusion: We identified ASE linked to blood pressure. Our results suggested that novel transcriptomic regulatory mechanisms involving allelic imbalance at specific SNPs may play a role in blood pressure regulation.