Abstract 13186: Rare and Low Frequency Variants Associated With Hypertension and Systolic Blood Pressure in Taiwan Chinese Families

Introduction: Hypertension (HTN) and related disorders constitute a major public-health burden. While genome-wide association studies have identified common variants for HTN, <2.5% of blood pressure (BP) variance has been explained. Hypothesis: Exome sequencing in families highly enriched for HTN will identify novel rare and low frequency variants associated with HTN and systolic blood pressure (SBP) with larger effect sizes. Methods: Exome sequencing in 150 hypertensive sib-pairs (300 subjects) and 300 unrelated controls identified 6,000 top variants which were then genotyped in SAPPHIRe families (N=1,100) and 1,100 unrelated matched controls. Single-variant analysis and four gene-based association tests (burden and SKAT tests using minor allele frequency thresholds of 1% [T1] and 5% [T5]) were performed for HTN and SBP. Bonferroni-adjusted significance level (5.4•10-5) was used. Results: Novel rare and low frequency variants with significant/suggestive association and biologic plausibility for roles in ...