A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood
Matthew O Goodman,
Joshua C. Bis,
Xiuqing O Guo,
Kent D Taylor,
Jennifer A Smith,
JoAnn E Manson,
Donald M Lloyd-Jones,
Ruth J.F. Loos,
Robert C. Kaplan,
Bruce M. Psaty,
Jerome I Rotter,
the NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium,
Posted 01 Nov 2021
medRxiv DOI: 10.1101/2021.10.31.21265717
Posted 01 Nov 2021
Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select one of multiple potential PRS based on the same GWAS, by optimizing the coefficient of variation across estimated PRS effect sizes in independent subsets of the training dataset. We combined the 3 selected trait-specific PRS as their unweighted sum, called "PRSsum". We evaluated PRS associations in an independent dataset of 39,035 individuals from eight cohort studies, to select the final, multi-ethnic, HTN-PRS. We estimated its association with prevalent and incident hypertension 4-6 years later. We studied hypertension development within HTN-PRS strata in a longitudinal, six-visit, longitudinal dataset of 3,087 self-identified Black and White participants from the CARDIA study. Finally, we evaluated the HTN-PRS association with clinical outcomes in 40,201 individuals from the MGB Biobank. Results: Compared to other race/ethnic backgrounds, African-Americans had higher average values of the HTN-PRS. The HTN-PRS was associated with prevalent hypertension (OR=2.10, 95% CI [1.99, 2.21], per one standard deviation (SD) of the PRS) across all participants, and in each race/ethnic background, with heterogeneity by background (p-value < 1.0x10-4). The lowest estimated effect size was in African Americans (OR=1.53, 95% CI [1.38, 1.69]). The HTN-PRS was associated with new onset hypertension among individuals with normal (respectively, elevated) BP at baseline: OR=1.71, 95% CI [1.55, 1.91] (OR=1.48, 95% CI [1.27, 1.71]). Association was further observed in age-stratified analysis. In CARDIA, Black participants with high HTN-PRS percentiles developed hypertension earlier than White participants with high HTN-PRS percentiles. The HTN-PRS was significantly associated with increased risk of coronary artery disease (OR=1.12), ischemic stroke (OR=1.15), type 2 diabetes (OR=1.19), and chronic kidney disease (OR=1.12), in the MGB Biobank. Conclusions: The multi-ethnic HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up across adulthood and is associated with clinical outcomes.
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