Faculty, Staff and Student Publications
Publication Date
6-2-2023
Journal
Nature Communications
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.
Keywords
Male, Female, Humans, Blood Pressure, Population Health, Risk Factors, Multifactorial Inheritance, Ethnicity, Genome-Wide Association Study, Genetic Predisposition to Disease
DOI
10.1038/s41467-023-38990-9
PMID
37268629
PMCID
PMC10238525
PubMedCentral® Posted Date
June 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Community Health and Preventive Medicine Commons, Medical Sciences Commons, Medicine and Health Commons, Oncology Commons, Race and Ethnicity Commons