Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study.
Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study.
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DOI：
10.1371/journal.pmed.1002525
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发表时间：
2018-03
期刊：
影响因子：
15.8
通讯作者：
Topol EJ
中科院分区：
文献类型：
--
作者：
Muse ED;Wineinger NE;Spencer EG;Peters M;Henderson R;Zhang Y;Barrett PM;Rivera SP;Wohlgemuth JG;Devlin JJ;Shiffman D;Topol EJ
心房颤动（AF）是最常见的心律失常，与卒中风险升高相关。改善对房颤最高风险患者的识别，以便在必要时进行适当的监测和治疗，对于降低房颤相关的发病率和死亡率至关重要。多个常见的单核苷酸多态性（SNP）与AF的终生风险明确相关。在当前的研究中，我们旨在前瞻性地验证先前未诊断的有AF风险的患者的AF遗传风险评分（GRS）。40岁或40岁以上的具有1个AF临床风险因素的个体，表现出AF症状，或首次诊断为AF，入组进行基因检测，并使用贴片监测仪或长期霍尔特监测仪进行动态心律监测（平均佩戴时间分别为10天21小时和13天18小时）。AF事件是通过ECG、贴片监测仪或长期霍尔特监测仪首次诊断的AF。根据12个遗传风险基因座的加权贡献确定每位参与者的AF GRS。在904名参与者中，85名表现出AF。他们的平均年龄为66.2岁（SD 11.8）; 38%的参与者为男性。在调整年龄、性别、吸烟状况、BMI、高血压、糖尿病、心力衰竭和既往心肌梗死后，AF GRS最高五分位数的参与者比最低五分位数的参与者更有可能发生AF事件（比值比3.11; 95% CI 1.27-7.58; p = 0.01）。研究的局限性包括种族同质的人群，有限的心律监测期，以及与AF相关的SNP的不断发现。对AF的GRS进行前瞻性评估，确定了AF风险升高的参与者，超出了既定的临床标准。因此，AF的GRS可以纳入整体风险评估，以更好地识别发生AF风险最高的患者，尽管需要在更大人群中进行进一步测试以证实这些发现。ClinicalTrials.gov NCT 01970969在前瞻性队列研究中，Eric Topol和同事验证了一种遗传风险评分，用于识别发生房颤风险最高的患者。心房颤动（AF）是一种常见的心律紊乱，可导致毁灭性的中风。虽然年龄、高血压和肥胖等临床因素会增加房颤的发生率，但房颤的几个遗传决定因素也起着一定的作用。在这里，我们评估了房颤遗传风险评分（GRS）识别心律监测时出现房颤最高可能性症状的个体的能力。入组年龄≥ 40岁且至少有1个AF临床风险因素的个体，这些个体表现为AF症状或心电图首次诊断为AF。对心电图上无房颤的患者进行贴片式或长期霍尔特心律监测，监测时间超过2周。从血液样本中分离DNA，并计算每位参与者的AF GRS。我们发现，AF GRS最高的个体在研究期间被诊断为AF的可能性是AF GRS最低的参与者的3倍。AF GRS可纳入整体风险评估策略，以更好地识别发生AF风险最高的患者。对于不明原因卒中患者，高AF GRS可能有助于指导诊断测试。在未来，具有高AF基因组风险的个体可能能够使用这些信息来帮助预防心律失常的发生。
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 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. Atrial fibrillation (AF) is a common heart rhythm disturbance that can lead to devastating strokes. While clinical factors such as age, high blood pressure, and obesity can increase the chances of developing AF, several genetic determinants of AF also play a role. Here we assessed the ability of a genetic risk score (GRS) for AF to identify individuals presenting with symptoms with the highest likelihood of AF on cardiac rhythm monitoring. Individuals 40 years of age or older with at least 1 clinical risk factor for AF presenting either with symptoms of AF or with the first diagnosis of AF on electrocardiogram were enrolled. A patch-based or long-term Holter cardiac rhythm monitor was fitted to individuals without AF on electrocardiogram, and they were monitored for upwards of 2 weeks. DNA was isolated from a blood sample, and an AF GRS was calculated for each participant. We found that individuals with the highest AF GRSs were 3 times more likely to be diagnosed with AF during the study than participants with the lowest AF GRSs. An AF GRS may be incorporated into an overall risk assessment strategy to better identify patients at the highest risk of developing AF. For patients with stroke of unknown origin, a high AF GRS may be helpful to guide diagnostic testing. In the future, individuals with high AF genomic risk may be able to use this information to help prevent the arrhythmia from occurring.
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影响因子：
30.8
作者：
Ellinor, Patrick T.;Lunetta, Kathryn L.;Glazer, Nicole L.;Pfeufer, Arne;Alonso, Alvaro;Chung, Mina K.;Sinner, Moritz F.;de Bakker, Paul I. W.;Mueller, Martina;Lubitz, Steven A.;Fox, Ervin;Darbar, Dawood;Smith, Nicholas L.;Smith, Jonathan D.;Schnabel, Renate B.;Soliman, Elsayed Z.;Rice, Kenneth M.;Van Wagoner, David R.;Beckmann, Britt-M;van Noord, Charlotte;Wang, Ke;Ehret, Georg B.;Rotter, Jerome I.;Hazen, Stanley L.;Steinbeck, Gerhard;Smith, Albert V.;Launer, Lenore J.;Harris, Tamara B.;Makino, Seiko;Nelis, Mari;Milan, David J.;Perz, Siegfried;Esko, Tonu;Koettgen, Anna;Moebus, Susanne;Newton-Cheh, Christopher;Li, Man;Moehlenkamp, Stefan;Wang, Thomas J.;Kao, W. H. Linda;Vasan, Ramachandran S.;Noethen, Markus M.;MacRae, Calum A.;Stricker, Bruno H. Ch;Hofman, Albert;Uitterlinden, Andre G.;Levy, Daniel;Boerwinkle, Eric;Metspalu, Andres;Topol, Eric J.;Chakravarti, Aravinda;Gudnason, Vilmundur;Psaty, Bruce M.;Roden, Dan M.;Meitinger, Thomas;Wichmann, H-Erich;Witteman, Jacqueline C. M.;Barnard, John;Arking, Dan E.;Benjamin, Emelia J.;Heckbert, Susan R.;Kaeaeb, Stefan
通讯作者：
Kaeaeb, Stefan
影响因子：
24
作者：
Kolek, Matthew J.;Graves, Amy J.;Darbar, Dawood
通讯作者：
Darbar, Dawood
DOI：
10.1253/circj.cj-16-0239
发表时间：
2016-04-25
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Alonso A;Norby FL
通讯作者：
Norby FL
影响因子：
1.9
作者：
Arboix A;Alió J
通讯作者：
Alió J
影响因子：
39.3
作者：
Everett BM;Cook NR;Conen D;Chasman DI;Ridker PM;Albert CM
通讯作者：
Albert CM