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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.021916 |
| _version_ | 1811310965404205056 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T10:09:40Z |
| format | Article |
| id | doaj.art-4df61ee4967e4e3c85259d214fe1e2ac |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T10:09:40Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-4df61ee4967e4e3c85259d214fe1e2ac2022-12-22T02:50:58ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-11-01102210.1161/JAHA.121.021916Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart FailureIshan Paranjpe0Noah L. Tsao1Jessica K. De Freitas2Renae Judy3Kumardeep Chaudhary4Iain S. Forrest5Suraj K. Jaladanki6Manish Paranjpe7Pranav Sharma8Benjamin S. Glicksberg9Jagat Narula10Ron Do11Scott M. Damrauer12Girish N. Nadkarni13The Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYDepartment of Surgery Perelman School of Medicine University of Pennsylvania Philadelphia PAMount Sinai Clinical Intelligence Center (MSCIC)Icahn School of Medicine at Mount Sinai New York NYDepartment of Surgery Perelman School of Medicine University of Pennsylvania Philadelphia PAThe Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYThe Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYThe Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYDivision of Health Science and Technology Harvard Medical School Boston MADrexel University College of Medicine Philadelphia PAMount Sinai Clinical Intelligence Center (MSCIC)Icahn School of Medicine at Mount Sinai New York NYZena and Michael A. Wiener Cardiovascular InstituteIcahn School of Medicine at Mount Sinai New York NYThe Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYDepartment of Surgery Perelman School of Medicine University of Pennsylvania Philadelphia PAThe Charles Bronfman Institute for Personalized MedicineIcahn School of Medicine at Mount Sinai New York NYBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.121.021916genomicsheart failurepersonalized medicinepolygenic risk score |
| spellingShingle | 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 Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease genomics heart failure personalized medicine polygenic risk score |
| 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 | genomics heart failure personalized medicine polygenic risk score |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.021916 |
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