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 validate...

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Autores principales:	Ishan Paranjpe, Noah L. Tsao, Jessica K. De Freitas, Renae Judy, Kumardeep Chaudhary, Iain S. Forrest, Suraj K. Jaladanki, Manish Paranjpe, Pranav Sharma, Benjamin S. Glicksberg, Jagat Narula, Ron Do, Scott M. Damrauer, Girish N. Nadkarni
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	genomics heart failure personalized medicine polygenic risk score Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/4df61ee4967e4e3c85259d214fe1e2ac
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spelling	oai:doaj.org-article:4df61ee4967e4e3c85259d214fe1e2ac2021-11-16T10:22:43ZDerivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure10.1161/JAHA.121.0219162047-9980https://doaj.org/article/4df61ee4967e4e3c85259d214fe1e2ac2021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.021916https://doaj.org/toc/2047-9980Background 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.Ishan ParanjpeNoah L. TsaoJessica K. De FreitasRenae JudyKumardeep ChaudharyIain S. ForrestSuraj K. JaladankiManish ParanjpePranav SharmaBenjamin S. GlicksbergJagat NarulaRon DoScott M. DamrauerGirish N. NadkarniWileyarticlegenomicsheart failurepersonalized medicinepolygenic risk scoreDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	genomics heart failure personalized medicine polygenic risk score Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	genomics heart failure personalized medicine polygenic risk score Diseases of the circulatory (Cardiovascular) system RC666-701 Ishan Paranjpe Noah L. Tsao Jessica K. De Freitas Renae Judy Kumardeep Chaudhary Iain S. Forrest Suraj K. Jaladanki Manish Paranjpe Pranav Sharma Benjamin S. Glicksberg Jagat Narula Ron Do Scott M. Damrauer Girish N. Nadkarni Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
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.
format	article
author	Ishan Paranjpe Noah L. Tsao Jessica K. De Freitas Renae Judy Kumardeep Chaudhary Iain S. Forrest Suraj K. Jaladanki Manish Paranjpe Pranav Sharma Benjamin S. Glicksberg Jagat Narula Ron Do Scott M. Damrauer Girish N. Nadkarni
author_facet	Ishan Paranjpe Noah L. Tsao Jessica K. De Freitas Renae Judy Kumardeep Chaudhary Iain S. Forrest Suraj K. Jaladanki Manish Paranjpe Pranav Sharma Benjamin S. Glicksberg Jagat Narula Ron Do Scott M. Damrauer Girish N. Nadkarni
author_sort	Ishan Paranjpe
title	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_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_sort	derivation and validation of genome‐wide polygenic score for ischemic heart failure
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/4df61ee4967e4e3c85259d214fe1e2ac
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Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure

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