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 language | English (US) |
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Article number | 3202 |
Journal | Nature communications |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Funding
This study was performed as a collaboration of the NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium. We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed and CCDG. TOPMed and CCDG acknowledgements, as well as descriptions, acknowledgements, and ethics statements of contributing studies are provided in Supplementary Note 3. TOPMed consortium researchers and their affiliations are listed in Supplementary Note 4. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. This research has been conducted using the UK Biobank Resource (application 81097). We would like to thank the participants and researchers from the UK Biobank who contributed or collected data. We thank Mass General Brigham Biobank for providing samples, genomic data, and health information data. The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. The All of Us Research Program would not be possible without the partnership of its participants. This research was supported by National Heart Lung and Blood Institute awards R01HL161012 (TS), R35HL135818 (SR), F32HL152555 (MOG). This study was performed as a collaboration of the NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium. We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed and CCDG. TOPMed and CCDG acknowledgements, as well as descriptions, acknowledgements, and ethics statements of contributing studies are provided in Supplementary Note . TOPMed consortium researchers and their affiliations are listed in Supplementary Note . The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. This research has been conducted using the UK Biobank Resource (application 81097). We would like to thank the participants and researchers from the UK Biobank who contributed or collected data. We thank Mass General Brigham Biobank for providing samples, genomic data, and health information data. The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. The All of Us Research Program would not be possible without the partnership of its participants. This research was supported by National Heart Lung and Blood Institute awards R01HL161012 (TS), R35HL135818 (SR), F32HL152555 (MOG).
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy