A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood

Abstract

In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called “PRSsum”, forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.

Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study

“…Given the higher frequency of White participants in the MVP, we hypothesized that the PRS would perform somewhat better in this population. Although our finding was unexpected, a previous study assessing the performance of the BP PRS in Black and White CARDIA participants showed that the Black participants in the high PRS percentiles developed hypertension earlier than the White participants in higher PRS percentiles when compared to their counterparts in lower PRS percentiles [ 37 ]. Given the limited number of studies with this type of data, it is difficult to determine whether this might be a statistical anomaly or whether genetic susceptibility could be more deterministic in Black participants.…”

“…Furthermore, because this study was conducted in a sample of two races of participants, we were able to evaluate the performance of the PRS in non-White participants, which have been underrepresented in genomics research. The PRSs used in this study were derived from the summary statistics of a large, multi-ancestry GWAS that were tested among 10,314 diverse participants using a novel approach and evaluated in 40,201 individuals [ 37 ]. Representing some of the first BP PRSs generated in diverse samples, our study demonstrates strong associations in non-White participants.…”

“…The current study leveraged previously constructed and validated multi-ancestry PRSs for SBP, DBP, and HTN [ 37 ]. In brief, the SBP and DBP PRSs were derived using summary statistics from BP GWAS of up to 318,891 participants of the Million Veteran Program (MVP) [ 20 ].…”

“…In this study, we hypothesized that genetic predisposition to high BP could help identify individuals in childhood who might be at higher risk for hypertension. We tested this hypothesis by leveraging recently validated multi-ancestry genome-wide PRSs for systolic BP (SBP), diastolic BP (DBP), and HTN [ 37 ]. We then examined the associations between these BP PRSs and hypertension development and midlife BP among a sample of two races of 1201 Bogalusa Heart Study (BHS) participants with up to 16 carefully collected measures of BP from childhood to midlife.…”

Genetic determinants of cardiometabolic and pulmonary phenotypes and obstructive sleep apnoea in HCHS/SOL

“…Still, we found in our recent work using summary statistics from large GWAS (hundreds of thousands of individuals) that PRS constructed based on GWAS in a population of a predominately European ancestry tend to generalize to Hispanics/Latinos, often with similar or only slightly attenuated performance. 70 , 71 If PRS have attenuated performance, we expect that estimated effect sizes will be biased towards the null compared to the effect sizes of optimal PRSs, rather than lead to false detections of associations. Second, the OSA GWAS that we used was based on ICD codes from a health care system, and is likely limited by under diagnosis of OSA.…”