Title | A polygenic risk score of atrial fibrillation improves prediction of lifetime risk for heart failure. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Alkis, T, Luo, X, Wall, K, Brody, J, Bartz, T, Chang, PP, Norby, FL, Hoogeveen, RC, Morrison, AC, Ballantyne, CM, Coresh, J, Boerwinkle, E, Psaty, BM, Shah, AM, Yu, B |
Journal | ESC Heart Fail |
Date Published | 2024 Jan 22 |
ISSN | 2055-5822 |
Abstract | <p><b>AIMS: </b>Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk-factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi-racial populations.</p><p><b>METHODS AND RESULTS: </b>Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31% cumulative incidence) HF cases developed over 30 years of follow-up. PRSs of AF, BMI, and CHD were associated with incident HF (P < 0.001), where PRS showed the strongest association [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.41-1.53]. Only the addition of PRS to the ARIC study HF risk equation improved C statistics for 10 year risk prediction from 0.812 to 0.829 (∆C: 0.017, 95% CI: 0.009-0.026). The PRS was associated with both incident HF with reduced ejection fraction (HR: 1.43, 95% CI: 1.27-1.60) and incident HF with preserved ejection fraction (HR: 1.46, 95% CI: 1.33-1.62). The associations between PRS and incident HF and its subtypes, as well as the improved risk prediction, were replicated in the ARIC study Blacks and the CHS Whites (P < 0.050). Protein analyses revealed that N-terminal pro-brain natriuretic peptide and other 98 proteins were associated with PRS .</p><p><b>CONCLUSIONS: </b>The PRS was associated with incident HF and its subtypes and had significant incremental value over an established HF risk prediction equation.</p> |
DOI | 10.1002/ehf2.14665 |
Alternate Journal | ESC Heart Fail |
PubMed ID | 38258344 |
Grant List | U01HL130114 / HL / NHLBI NIH HHS / United States R01HL120393 / HL / NHLBI NIH HHS / United States R01HL103612 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States K24HL152008 / HL / NHLBI NIH HHS / United States R01HL150342 / HL / NHLBI NIH HHS / United States R01HL143224 / HL / NHLBI NIH HHS / United States R01HL135008 / HL / NHLBI NIH HHS / United States R01HL160793 / HL / NHLBI NIH HHS / United States R01HL148218 / HL / NHLBI NIH HHS / United States R01HL141824 / HL / NHLBI NIH HHS / United States R01HL134320 / HL / NHLBI NIH HHS / United States R01HL105756 / HL / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL059367 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States UL1RR025005 / NH / NIH HHS / United States HHSN268200625226C / NH / NIH HHS / United States HHSN268201700005I / NH / NIH HHS / United States HHSN268201700004I / NH / NIH HHS / United States HHSN268201700003I / NH / NIH HHS / United States HHSN268201700002I / NH / NIH HHS / United States HHSN268201700001I / NH / NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States R01AG023629 / AG / NIA NIH HHS / United States |