Abstract

ObjectiveHypertension is more prevalent in African Americans (AA) than other ethnic groups. Genome-wide association studies (GWAS) have identified loci associated with hypertension and other cardio-metabolic traits like type 2 diabetes, coronary artery disease, and body mass index (BMI), however the AA population is underrepresented in these studies. In this study, we examined a large AA cohort for the generalizability of 14 Metabochip array SNPs with previously reported European hypertension associations.MethodsTo evaluate associations, we analyzed genotype data of 14 SNPs for their associations with a diagnosis of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in a case-control study of an AA population (N = 9,534). We also performed an age-stratified analysis (>30, 30≥59 and ≥60 years) following the hypertension definition described by the 8th Joint National Committee (JNC). Associations were adjusted for BMI, age, age2, sex, clinical confounders, and genetic ancestry using multivariable regression models to estimate odds ratios (ORs) and beta-coefficients. Analyses stratified by sex were also conducted. Meta-analyses (including both BioVU and COGENT-BP cohorts) were performed using a random-effects model.ResultsWe found rs880315 to be associated with systolic hypertension (SBP≥140 mmHg) in the entire cohort (OR = 1.14, p = 0.003) and within women only (OR = 1.16, p = 0.012). Variant rs17080093 associated with lower SBP and DBP (β = -2.99, p = 0.0352 and - β = 1.69, p = 0.0184) among younger individuals, particularly in younger women (β = -3.92, p = 0.0025 and β = -1.87, p = 0.0241 for SBP and DBP respectively). SNP rs1530440 associated with higher SBP and DBP measurements (younger individuals β = 4.1, p = 0.039 and β = 2.5, p = 0.043 for SBP and DBP; (younger women β = 4.5, p = 0.025 and β = 2.9, p = 0.028 for SBP and DBP), and hypertension risk in older women (OR = 1.4, p = 0.050). rs16948048 increases hypertension risk in younger individuals (OR = 1.31, p = 0.011). Among mid-age women rs880315 associated with higher risk of hypertension (OR = 1.20, p = 0.027). rs1361831 associated with DBP (β = -1.96, p = 0.02) among individuals older than 60 years. rs3096277 increases hypertension risk among older individuals (OR = 1.26 p = 0.0015), however, this variant also reduces SBP among younger women (β = -2.63, p = 0.0102).ConclusionThese findings suggest that European-descent and AA populations share genetic loci that contribute to blood pressure traits and hypertension. However, the OR and beta-coefficient estimates differ, and some are age-dependent. Additional genetic studies of hypertension in AA are warranted to identify new loci associated with hypertension and blood pressure traits in this population.

Highlights

  • Elevated blood pressure, or hypertension [1], is one of the major preventable risk factors for heart disease, as well as a leading contributor to mortality globally [2]

  • We found rs880315 to be associated with systolic hypertension (SBP 140 mmHg) in the entire cohort (OR = 1.14, p = 0.003) and within women only (OR = 1.16, p = 0.012)

  • Variant rs17080093 associated with lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) (β = -2.99, p = 0.0352 and - β = 1.69, p = 0.0184) among younger individuals, in younger women (β = -3.92, p = 0.0025 and β = -1.87, p = 0.0241 for SBP and DBP respectively)

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Summary

Introduction

Elevated blood pressure, or hypertension [1], is one of the major preventable risk factors for heart disease, as well as a leading contributor to mortality globally [2]. It affects approximately 50 million individuals in the US and accounts for 4.5% of the global burden of all diseases. The National Health and Nutrition Examination Survey (NHANES 2011–2012), conducted by the Centers for Disease Control (CDC), described the highest prevalence of hypertension in the US to be among AfricanAmerican (AA) adults (42.1%), compared with non-Hispanic whites (28.0%), Hispanic (26.0%), and non-Hispanic Asian (24.7%) adults. Much of the differences in hypertension prevalence in AA remain unexplained [14]

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