Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

Nuzulul Kurniansyah, Matthew O. Goodman, Alyna T. Khan, Jiongming Wang, Elena Feofanova, Joshua C. Bis, Kerri L. Wiggins, Jennifer E. Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J. Lin, Shih-Jen Hwang, Yan Gao, Kendra Young, Gregory L. Kinney, Jennifer A. Smith, Bing Yu, Simin Liu, Sylvia Wassertheil-Smoller, JoAnn E. Manson, Xiaofeng Zhu, Yii- Der Ida Chen, I-Te Lee, C. Charles Gu, Donald M. Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M. Psaty, Donna K. Arnett, Carmen R. Isasi, Stephen S. Rich, Robert C. Kaplan, Susan Redline, Braxton D. Mitchell, Nora Franceschini, Daniel Levy, Jerome I. Rotter, Alanna C. Morrison and Tamar Sofer ()
Additional contact information
Nuzulul Kurniansyah: Brigham and Women’s Hospital
Matthew O. Goodman: Brigham and Women’s Hospital
Alyna T. Khan: University of Washington
Jiongming Wang: University of Michigan
Elena Feofanova: The University of Texas Health Science Center at Houston
Joshua C. Bis: University of Washington
Kerri L. Wiggins: University of Washington
Jennifer E. Huffman: VA Boston Healthcare System
Tanika Kelly: Tulane University School of Public Health and Tropical Medicine
Tali Elfassy: University of Miami Miller School of Medicine
Xiuqing Guo: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Walter Palmas: Columbia University Medical Center
Henry J. Lin: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Shih-Jen Hwang: Lung and Blood Institute
Yan Gao: University of Mississippi Medical Center
Kendra Young: Colorado School of Public Health
Gregory L. Kinney: Colorado School of Public Health
Jennifer A. Smith: University of Michigan School of Public Health
Bing Yu: The University of Texas Health Science Center at Houston
Simin Liu: Brown University
Sylvia Wassertheil-Smoller: Albert Einstein College of Medicine
JoAnn E. Manson: Brigham and Women’s Hospital
Xiaofeng Zhu: Case Western Reserve University
Yii- Der Ida Chen: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
I-Te Lee: Taichung Veterans General Hospital
C. Charles Gu: Washington University School of Medicine
Donald M. Lloyd-Jones: Northwestern University
Sebastian Zöllner: University of Michigan
Myriam Fornage: The University of Texas Health Science Center at Houston
Charles Kooperberg: Fred Hutchinson Cancer Research Center
Adolfo Correa: University of Mississippi Medical Center
Bruce M. Psaty: University of Washington
Donna K. Arnett: University of South Carolina
Carmen R. Isasi: Albert Einstein College of Medicine
Stephen S. Rich: University of Virginia School of Medicine
Robert C. Kaplan: Albert Einstein College of Medicine
Susan Redline: Brigham and Women’s Hospital
Braxton D. Mitchell: University of Maryland School of Medicine
Nora Franceschini: University of North Carolina
Daniel Levy: Lung and Blood Institute
Jerome I. Rotter: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Alanna C. Morrison: The University of Texas Health Science Center at Houston
Tamar Sofer: Brigham and Women’s Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Date: 2023
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DOI: 10.1038/s41467-023-38990-9

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