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Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure

BACKGROUND: Despite advances in cardiovascular disease and risk factor management, mortality from ischemic heart failure (HF) in patients with coronary artery disease (CAD) remains high. Given the partial role of genetics in HF and lack of reliable risk stratification tools, we developed and validat...

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Autores principales: Paranjpe, Ishan, Tsao, Noah L., De Freitas, Jessica K., Judy, Renae, Chaudhary, Kumardeep, Forrest, Iain S., Jaladanki, Suraj K., Paranjpe, Manish, Sharma, Pranav, Glicksberg, Benjamin S., Narula, Jagat, Do, Ron, Damrauer, Scott M., Nadkarni, Girish N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751935/
https://www.ncbi.nlm.nih.gov/pubmed/34713709
http://dx.doi.org/10.1161/JAHA.121.021916
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author Paranjpe, Ishan
Tsao, Noah L.
De Freitas, Jessica K.
Judy, Renae
Chaudhary, Kumardeep
Forrest, Iain S.
Jaladanki, Suraj K.
Paranjpe, Manish
Sharma, Pranav
Glicksberg, Benjamin S.
Narula, Jagat
Do, Ron
Damrauer, Scott M.
Nadkarni, Girish N.
author_facet Paranjpe, Ishan
Tsao, Noah L.
De Freitas, Jessica K.
Judy, Renae
Chaudhary, Kumardeep
Forrest, Iain S.
Jaladanki, Suraj K.
Paranjpe, Manish
Sharma, Pranav
Glicksberg, Benjamin S.
Narula, Jagat
Do, Ron
Damrauer, Scott M.
Nadkarni, Girish N.
author_sort Paranjpe, Ishan
collection PubMed
description BACKGROUND: Despite advances in cardiovascular disease and risk factor management, mortality from ischemic heart failure (HF) in patients with coronary artery disease (CAD) remains high. Given the partial role of genetics in HF and lack of reliable risk stratification tools, we developed and validated a polygenic risk score for HF in patients with CAD, which we term HF‐PRS. METHODS AND RESULTS: Using summary statistics from a recent genome‐wide association study for HF, we developed candidate PRSs in the Mount Sinai BioMe CAD patient cohort (N=6274) by using the pruning and thresholding method and LDPred. We validated the best score in the Penn Medicine BioBank (N=7250) and performed a subgroup analysis in a high‐risk cohort who had undergone coronary catheterization. We observed a significant association between HF‐PRS score and ischemic HF even after adjusting for evidence of obstructive CAD in patients of European ancestry in both BioMe (odds ratio [OR], 1.14 per SD; 95% CI, 1.05–1.24; P=0.003) and Penn Medicine BioBank (OR, 1.07 per SD; 95% CI, 1.01–1.13; P=0.016). In European patients with CAD in Penn Medicine BioBank who had undergone coronary catheterization, individuals in the top 10th percentile of PRS had a 2‐fold increased odds of ischemic HF (OR, 2.0; 95% CI, 1.1–3.7; P=0.02) compared with the bottom 10th percentile. CONCLUSIONS: A PRS for HF enables risk stratification in patients with CAD. Future prospective studies aimed at demonstrating clinical utility are warranted for adoption in the patient setting.
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spelling pubmed-87519352022-01-14 Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure Paranjpe, Ishan Tsao, Noah L. De Freitas, Jessica K. Judy, Renae Chaudhary, Kumardeep Forrest, Iain S. Jaladanki, Suraj K. Paranjpe, Manish Sharma, Pranav Glicksberg, Benjamin S. Narula, Jagat Do, Ron Damrauer, Scott M. Nadkarni, Girish N. J Am Heart Assoc Original Research BACKGROUND: Despite advances in cardiovascular disease and risk factor management, mortality from ischemic heart failure (HF) in patients with coronary artery disease (CAD) remains high. Given the partial role of genetics in HF and lack of reliable risk stratification tools, we developed and validated a polygenic risk score for HF in patients with CAD, which we term HF‐PRS. METHODS AND RESULTS: Using summary statistics from a recent genome‐wide association study for HF, we developed candidate PRSs in the Mount Sinai BioMe CAD patient cohort (N=6274) by using the pruning and thresholding method and LDPred. We validated the best score in the Penn Medicine BioBank (N=7250) and performed a subgroup analysis in a high‐risk cohort who had undergone coronary catheterization. We observed a significant association between HF‐PRS score and ischemic HF even after adjusting for evidence of obstructive CAD in patients of European ancestry in both BioMe (odds ratio [OR], 1.14 per SD; 95% CI, 1.05–1.24; P=0.003) and Penn Medicine BioBank (OR, 1.07 per SD; 95% CI, 1.01–1.13; P=0.016). In European patients with CAD in Penn Medicine BioBank who had undergone coronary catheterization, individuals in the top 10th percentile of PRS had a 2‐fold increased odds of ischemic HF (OR, 2.0; 95% CI, 1.1–3.7; P=0.02) compared with the bottom 10th percentile. CONCLUSIONS: A PRS for HF enables risk stratification in patients with CAD. Future prospective studies aimed at demonstrating clinical utility are warranted for adoption in the patient setting. John Wiley and Sons Inc. 2021-10-29 /pmc/articles/PMC8751935/ /pubmed/34713709 http://dx.doi.org/10.1161/JAHA.121.021916 Text en © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Paranjpe, Ishan
Tsao, Noah L.
De Freitas, Jessica K.
Judy, Renae
Chaudhary, Kumardeep
Forrest, Iain S.
Jaladanki, Suraj K.
Paranjpe, Manish
Sharma, Pranav
Glicksberg, Benjamin S.
Narula, Jagat
Do, Ron
Damrauer, Scott M.
Nadkarni, Girish N.
Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title_full Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title_fullStr Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title_full_unstemmed Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title_short Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
title_sort derivation and validation of genome‐wide polygenic score for ischemic heart failure
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751935/
https://www.ncbi.nlm.nih.gov/pubmed/34713709
http://dx.doi.org/10.1161/JAHA.121.021916
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