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

Nuzulul Kurniansyah, Matthew O. Goodman, Tanika N. Kelly, Tali Elfassy, Kerri L. Wiggins, Joshua C. Bis, Xiuqing Guo, Walter Palmas, Kent D. Taylor, Henry J. Lin, Jeffrey Haessler, Yan Gao, Daichi Shimbo, Jennifer A. Smith, Bing Yu, Elena V. Feofanova, Roelof A. J. Smit, Zhe Wang, Shih-Jen Hwang, Simin Liu, Sylvia Wassertheil-Smoller, JoAnn E. Manson, Donald M. Lloyd-Jones, Stephen S. Rich, Ruth J. F. Loos, Susan Redline, Adolfo Correa, Charles Kooperberg, Myriam Fornage, Robert C. Kaplan, Bruce M. Psaty, Jerome I. Rotter, Donna K. Arnett, Alanna C. Morrison, Nora Franceschini, Daniel Levy and Tamar Sofer ()
Additional contact information
Nuzulul Kurniansyah: Brigham and Women’s Hospital
Matthew O. Goodman: Brigham and Women’s Hospital
Tanika N. Kelly: Tulane University School of Public Health and Tropical Medicine
Tali Elfassy: University of Miami Miller School of Medicine
Kerri L. Wiggins: University of Washington
Joshua C. Bis: University of Washington
Xiuqing Guo: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Walter Palmas: Columbia University Medical Center
Kent D. Taylor: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Henry J. Lin: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Jeffrey Haessler: Fred Hutchinson Cancer Center
Yan Gao: University of Mississippi Medical Center
Daichi Shimbo: Columbia University Irving Medical Center
Jennifer A. Smith: University of Michigan School of Public Health
Bing Yu: University of Texas Health Science Center at Houston
Elena V. Feofanova: University of Texas Health Science Center at Houston
Roelof A. J. Smit: Icahn School of Medicine at Mount Sinai
Zhe Wang: Icahn School of Medicine at Mount Sinai
Shih-Jen Hwang: Boston University
Simin Liu: Brown University
Sylvia Wassertheil-Smoller: Albert Einstein College of Medicine
JoAnn E. Manson: Harvard Medical School
Donald M. Lloyd-Jones: Northwestern University
Stephen S. Rich: University of Virginia School of Medicine
Ruth J. F. Loos: Icahn School of Medicine at Mount Sinai
Susan Redline: Brigham and Women’s Hospital
Adolfo Correa: University of Mississippi Medical Center
Charles Kooperberg: Fred Hutchinson Cancer Center
Myriam Fornage: University of Texas Health Science Center at Houston
Robert C. Kaplan: Fred Hutchinson Cancer Center
Bruce M. Psaty: University of Washington
Jerome I. Rotter: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Donna K. Arnett: University of Kentucky
Alanna C. Morrison: University of Texas Health Science Center at Houston
Nora Franceschini: University of North Carolina
Daniel Levy: Lung and Blood Institute
Tamar Sofer: Brigham and Women’s Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31080-2

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