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12 results on '"Lubitz, Steve A."'

1. Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis

Author

Small, Aeron M., primary, Melloni, Giorgio E. M., additional, Kamanu, Frederick K., additional, Bergmark, Brian A., additional, Bonaca, Marc P., additional, O’Donoghue, Michelle L., additional, Giugliano, Robert P., additional, Scirica, Benjamin M., additional, Bhatt, Deepak, additional, Antman, Elliott M., additional, Raz, Itamar, additional, Wiviott, Stephen D., additional, Truong, Buu, additional, Wilson, Peter W. F., additional, Cho, Kelly, additional, O’Donnell, Christopher J., additional, Braunwald, Eugene, additional, Lubitz, Steve A., additional, Ellinor, Patrick, additional, Peloso, Gina M., additional, Ruff, Christian T., additional, Sabatine, Marc S., additional, Natarajan, Pradeep, additional, and Marston, Nicholas A., additional

Published
2024
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2. Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention

Author

Marston, Nicholas A., primary, Pirruccello, James P., additional, Melloni, Giorgio E. M., additional, Koyama, Satoshi, additional, Kamanu, Frederick K., additional, Weng, Lu-Chen, additional, Roselli, Carolina, additional, Kamatani, Yoichiro, additional, Komuro, Issei, additional, Aragam, Krishna G., additional, Butterworth, Adam S., additional, Ito, Kaoru, additional, Lubitz, Steve A., additional, Ellinor, Patrick T., additional, Sabatine, Marc S., additional, and Ruff, Christian T., additional

Published
2022
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3. Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention

Author

Marston, Nicholas A, Pirruccello, James P, Melloni, Giorgio EM, Koyama, Satoshi, Kamanu, Frederick K, Weng, Lu-Chen, Roselli, Carolina, Kamatani, Yoichiro, Komuro, Issei, Aragam, Krishna G, Butterworth, Adam S, Ito, Kaoru, Lubitz, Steve A, Ellinor, Patrick T, Sabatine, Marc S, Ruff, Christian T, and Apollo - University of Cambridge Repository

Subjects
Myocardial Infarction, Coronary Artery Disease, Middle Aged, Atherosclerosis, Risk Assessment, Cohort Studies, Primary Prevention, Young Adult, Cardiovascular Diseases, Risk Factors, Humans, Female, Longitudinal Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract

ImportanceThe clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.ObjectiveTo investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.Design, Setting, and ParticipantsThis was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.ExposuresPolygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (Main Outcomes and MeasuresMyocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).ResultsA total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age 60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction Conclusions and RelevanceResults of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.

Published
2023

6. Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

Author

El Rouby, Nihal, primary, Rodrigues Marcatto, Leiliane, additional, Claudio, Karla, additional, Camargo Tavares, Letícia, additional, Steiner, Heidi, additional, Botton, Marianna R., additional, Lubitz, Steve A., additional, Fallon, Echo N., additional, Yee, Kevin, additional, Kaye, Justin, additional, Scott, Stuart A., additional, Karnes, Jason, additional, Caleb Junior de Lima Santos, Paulo, additional, Duconge, Jorge, additional, and Cavallari, Larisa H., additional

Published
2020
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7. Physiology as a Lingua Franca for Clinical Machine Learning

Author

Sarma, Gopal P., primary, Reinertsen, Erik, additional, Aguirre, Aaron, additional, Anderson, Chris, additional, Batra, Puneet, additional, Choi, Seung-Hoan, additional, Di Achille, Paolo, additional, Diamant, Nathaniel, additional, Ellinor, Patrick, additional, Emdin, Connor, additional, Fahed, Akl C., additional, Friedman, Samuel, additional, Harrington, Lia, additional, Ho, Jennifer E., additional, Khera, Amit V., additional, Khurshid, Shaan, additional, Klarqvist, Marcus, additional, Lubitz, Steve, additional, Philippakis, Anthony, additional, Pirruccello, James, additional, Reeder, Christopher, additional, Stultz, Collin, additional, and Westover, Brandon, additional

Published
2020
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8. Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos.

Author

El Rouby, Nihal, Rodrigues Marcatto, Leiliane, Claudio, Karla, Camargo Tavares, Letícia, Steiner, Heidi, Botton, Marianna R., Lubitz, Steve A., Fallon, Echo N., Yee, Kevin, Kaye, Justin, Scott, Stuart A., Karnes, Jason, Caleb Junior de Lima Santos, Paulo, Duconge, Jorge, and Cavallari, Larisa H.

Subjects
HISPANIC Americans, MULTIPLE regression analysis, WARFARIN
Abstract

We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.‐1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10−16; β = −0.21, P = 4.7 × 10−7, respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10−4; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10−16), CYP2C9 (β = −0.07, P = 5.6 × 10−10), and CYP4F2 (β = 0.03, P = 3 × 10−3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43–46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin‐treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil. [ABSTRACT FROM AUTHOR]

Published
2021
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10. Physiology as a Lingua Franca for Clinical Machine Learning

Author

Aguirre, Aaron, Anderson, Chris, Batra, Puneet, Choi, Seung-Hoan, Di Achille, Paolo, Diamant, Nathaniel, Ellinor, Patrick, Emdin, Connor, Fahed, Akl C., Friedman, Samuel, Harrington, Lia, Ho, Jennifer E., Khera, Amit V., Khurshid, Shaan, Klarqvist, Marcus, Lubitz, Steve, Philippakis, Anthony, Pirruccello, James, Reeder, Christopher, Stultz, Collin, Westover, Brandon, Sarma, Gopal P., and Reinertsen, Erik

Published
2020
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11. Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study)

Author

Kim, Eun-Jeong, primary, Yin, Xiaoyan, additional, Fontes, João D., additional, Magnani, Jared W., additional, Lubitz, Steve A., additional, McManus, David D., additional, Seshadri, Sudha, additional, Vasan, Ramachandran S., additional, Ellinor, Patrick T., additional, Larson, Martin G., additional, Benjamin, Emelia J., additional, and Rienstra, Michiel, additional

Published
2016
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12. Multi-site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos.

Author

El Rouby N, Rodrigues Marcatto L, Claudio K, Camargo Tavares L, Steiner H, Botton MR, Lubitz SA, Fallon EN, Yee K, Kaye J, Scott SA, Karnes J, Caleb Junior de Lima Santos P, Duconge J, and Cavallari LH

Subjects
Aged, Brazil, Cohort Studies, Cytochrome P-450 CYP2C9 genetics, Cytochrome P-450 CYP2C9 metabolism, Cytochrome P450 Family 4 genetics, Cytochrome P450 Family 4 metabolism, Dose-Response Relationship, Drug, Female, Gene Frequency, Hispanic or Latino statistics & numerical data, Humans, Male, Middle Aged, NAD(P)H Dehydrogenase (Quinone) genetics, NAD(P)H Dehydrogenase (Quinone) metabolism, Pharmacogenomic Testing statistics & numerical data, Pharmacogenomic Variants, United States, Vitamin K Epoxide Reductases genetics, Vitamin K Epoxide Reductases metabolism, Anticoagulants administration & dosage, Biological Variation, Population genetics, Hispanic or Latino genetics, Thromboembolism drug therapy, Warfarin administration & dosage
Abstract

We conducted a multi-site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.-1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = -0.29, P < 2.0 × 10 -16 ; β = -0.21, P = 4.7 × 10 -7 , respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10 -4 ; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = -0.14, P = 2.0 × 10 -16 ), CYP2C9 (β = -0.07, P = 5.6 × 10 -10 ), and CYP4F2 (β = 0.03, P = 3 × 10 -3 ), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43-46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin-treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society of Clinical Pharmacology and Therapeutics.)

Published
2021
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