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 LiuSylvia Wassertheil-Smoller, Jo Ann 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, Tamar Sofer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3202
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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