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

• Published in: Nature communications Vol. 13; no. 1; pp. 3549 - 13
• Main Authors: Kurniansyah, Nuzulul, Goodman, Matthew O., Kelly, Tanika N., Elfassy, Tali, Wiggins, Kerri L., Bis, Joshua C., Guo, Xiuqing, Palmas, Walter, Taylor, Kent D., Lin, Henry J., Haessler, Jeffrey, Gao, Yan, Shimbo, Daichi, Smith, Jennifer A., Yu, Bing, Feofanova, Elena V., Smit, Roelof A. J., Wang, Zhe, Hwang, Shih-Jen, Liu, Simin, Wassertheil-Smoller, Sylvia, Manson, JoAnn E., Lloyd-Jones, Donald M., Rich, Stephen S., Loos, Ruth J. F., Redline, Susan, Correa, Adolfo, Kooperberg, Charles, Fornage, Myriam, Kaplan, Robert C., Psaty, Bruce M., Rotter, Jerome I., Arnett, Donna K., Morrison, Alanna C., Franceschini, Nora, Levy, Daniel, Sofer, Tamar
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 631/208/721; 692/699/75/243; Adult; Blood pressure; Cardiovascular disease; Coefficient of variation; Coronary artery; Coronary artery disease; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Genetic markers; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risks; Heart diseases; Humanities and Social Sciences; Humans; Hypertension; Hypertension - epidemiology; Hypertension - genetics; Ischemia; Kidney diseases; multidisciplinary; Multifactorial Inheritance - genetics; Polygenic inheritance; Prevalence; Risk; Risk assessment; Risk Factors; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31080-2

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. Polygenic risk scores have potential to predict an individual’s risk of disease based on genetic markers. Here, the authors develop a polygenic risk score for hypertension and test it in a multi-ethnic cohort, finding that the score is associated with higher likelihood of hypertension development 4-6 years later.