Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study

Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidit...

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Published inPLoS medicine Vol. 15; no. 3; p. e1002525
Main Authors Muse, Evan D, Wineinger, Nathan E, Spencer, Emily G, Peters, Melissa, Henderson, Riley, Zhang, Yunyue, Barrett, Paddy M, Rivera, Steven P, Wohlgemuth, Jay G, Devlin, James J, Shiffman, Dov, Topol, Eric J
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 13.03.2018
Public Library of Science (PLoS)
Subjects
Adhesion tests
Aged
Aminopeptidases - genetics
Analysis
Arrhythmia
Atrial fibrillation
Atrial Fibrillation - complications
Atrial Fibrillation - diagnosis
Atrial Fibrillation - genetics
Body mass
Cardiovascular disease
Caveolin 1 - genetics
Cerebral infarction
Cohort analysis
Cohort Studies
Diabetes mellitus
Diagnosis
Echocardiography
EKG
Electrocardiography
Electrocardiography, Ambulatory - methods
Female
Fibrillation
Genetic aspects
Genetic screening
Genetic Testing - methods
Health risk assessment
Health risks
Heart diseases
Homeobox Protein PITX2
Homeodomain Proteins - genetics
Humans
Male
Medicine and Health Sciences
Middle Aged
Morbidity
Myocardial infarction
Patients
Physical Sciences
Polymorphism, Single Nucleotide
Prospective Studies
Research and Analysis Methods
Risk assessment
Risk Assessment - methods
Risk Factors
Single-nucleotide polymorphism
Small-Conductance Calcium-Activated Potassium Channels - genetics
Smoking
Stroke - etiology
Stroke - prevention & control
Systematic review
Time Factors
Transcription Factors - genetics
La Jolla California
California
United States > US
San Juan Capistrano California
Online AccessGet full text

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Abstract Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. ClinicalTrials.gov NCT01970969.
AbstractList Background Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Methods and findings Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Conclusions Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. Trial registration ClinicalTrials.gov NCT01970969
Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. ClinicalTrials.gov NCT01970969.
Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Trial registration
BACKGROUND:Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. METHODS AND FINDINGS:Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. CONCLUSIONS:Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. TRIAL REGISTRATION:ClinicalTrials.gov NCT01970969.
In prospective cohort study, Eric Topol and colleague validate a genetic risk score for identification of patients at the highest risk of developing atrial fibrillation.
Background Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. Methods and findings Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. Conclusions Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. Trial registration ClinicalTrials.gov NCT01970969
BACKGROUNDAtrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF.METHODS AND FINDINGSIndividuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF.CONCLUSIONSProspective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings.TRIAL REGISTRATIONClinicalTrials.gov NCT01970969.
Audience Academic
Author Peters, Melissa
Barrett, Paddy M
Wineinger, Nathan E
Rivera, Steven P
Muse, Evan D
Wohlgemuth, Jay G
Devlin, James J
Shiffman, Dov
Topol, Eric J
Spencer, Emily G
Henderson, Riley
Zhang, Yunyue
AuthorAffiliation University of Oxford, UNITED KINGDOM
1 Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, California, United States of America
3 Quest Diagnostics, San Juan Capistrano, California, United States of America
2 Division of Cardiovascular Disease, Scripps Clinic–Scripps Health, La Jolla, California, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29534064$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright COPYRIGHT 2018 Public Library of Science
2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Muse ED, Wineinger NE, Spencer EG, Peters M, Henderson R, Zhang Y, et al. (2018) Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study. PLoS Med 15(3): e1002525. https://doi.org/10.1371/journal.pmed.1002525
2018 Muse et al 2018 Muse et al
2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Muse ED, Wineinger NE, Spencer EG, Peters M, Henderson R, Zhang Y, et al. (2018) Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study. PLoS Med 15(3): e1002525. https://doi.org/10.1371/journal.pmed.1002525
Copyright_xml – notice: COPYRIGHT 2018 Public Library of Science
– notice: 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Muse ED, Wineinger NE, Spencer EG, Peters M, Henderson R, Zhang Y, et al. (2018) Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study. PLoS Med 15(3): e1002525. https://doi.org/10.1371/journal.pmed.1002525
– notice: 2018 Muse et al 2018 Muse et al
– notice: 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Muse ED, Wineinger NE, Spencer EG, Peters M, Henderson R, Zhang Y, et al. (2018) Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study. PLoS Med 15(3): e1002525. https://doi.org/10.1371/journal.pmed.1002525
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JGW is an employee of Quest Diagnostics and receives stock and stock options from Quest Diagnostics. SPR, JJD and DS are employees of Quest Diagnostics.
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Snippet Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of...
Background Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification...
BACKGROUNDAtrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification...
In prospective cohort study, Eric Topol and colleague validate a genetic risk score for identification of patients at the highest risk of developing atrial...
BACKGROUND:Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification...
Background Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification...
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SubjectTerms Adhesion tests
Aged
Aminopeptidases - genetics
Analysis
Arrhythmia
Atrial fibrillation
Atrial Fibrillation - complications
Atrial Fibrillation - diagnosis
Atrial Fibrillation - genetics
Body mass
Cardiovascular disease
Caveolin 1 - genetics
Cerebral infarction
Cohort analysis
Cohort Studies
Diabetes mellitus
Diagnosis
Echocardiography
EKG
Electrocardiography
Electrocardiography, Ambulatory - methods
Female
Fibrillation
Genetic aspects
Genetic screening
Genetic Testing - methods
Health risk assessment
Health risks
Heart diseases
Homeobox Protein PITX2
Homeodomain Proteins - genetics
Humans
Male
Medicine and Health Sciences
Middle Aged
Morbidity
Myocardial infarction
Patients
Physical Sciences
Polymorphism, Single Nucleotide
Prospective Studies
Research and Analysis Methods
Risk assessment
Risk Assessment - methods
Risk Factors
Single-nucleotide polymorphism
Small-Conductance Calcium-Activated Potassium Channels - genetics
Smoking
Stroke - etiology
Stroke - prevention & control
Systematic review
Time Factors
Transcription Factors - genetics
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Title Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study
URI https://www.ncbi.nlm.nih.gov/pubmed/29534064
https://www.proquest.com/docview/2025699228/abstract/
https://search.proquest.com/docview/2013785728
https://pubmed.ncbi.nlm.nih.gov/PMC5849279
https://doaj.org/article/d701d336108445adbdc4280560031ae0
http://dx.doi.org/10.1371/journal.pmed.1002525
Volume 15
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