학술논문
Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups
Document Type
article
Author
Kurniansyah, Nuzulul; Goodman, Matthew O; Khan, Alyna T; Wang, Jiongming; Feofanova, Elena; Bis, Joshua C; Wiggins, Kerri L; Huffman, Jennifer E; Kelly, Tanika; Elfassy, Tali; Guo, Xiuqing; Palmas, Walter; Lin, Henry J; Hwang, Shih-Jen; Gao, Yan; Young, Kendra; Kinney, Gregory L; Smith, Jennifer A; Yu, Bing; Liu, Simin; Wassertheil-Smoller, Sylvia; Manson, JoAnn E; Zhu, Xiaofeng; Chen, Yii-Der Ida; Lee, I-Te; Gu, C Charles; Lloyd-Jones, Donald M; Zöllner, Sebastian; Fornage, Myriam; Kooperberg, Charles; Correa, Adolfo; Psaty, Bruce M; Arnett, Donna K; Isasi, Carmen R; Rich, Stephen S; Kaplan, Robert C; Redline, Susan; Mitchell, Braxton D; Franceschini, Nora; Levy, Daniel; Rotter, Jerome I; Morrison, Alanna C; Sofer, Tamar
Source
Nature Communications. 14(1)
Subject
Language
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.