A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study).
A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study).
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DOI：
10.1093/europace/euad320
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发表时间：
2023-11-02
期刊：
影响因子：
6.1
通讯作者：
Gudmundsdottir, Valborg
中科院分区：
文献类型：
--
作者：
Jonmundsson, Thorarinn;Steindorsdottir, Anna E.;Austin, Thomas R.;Frick, Elisabet A.;Axelsson, Gisli T.;Launer, Lenore;Psaty, Bruce M.;Loureiro, Joseph;Orth, Anthony P.;Aspelund, Thor;Emilsson, Valur;Floyd, James S.;Jennings, Lori;Gudnason, Vilmundur;Gudmundsdottir, Valborg
房颤（AF）与合并症和死亡率的高风险相关。我们的目的是在前瞻性人群年龄、基因/环境易感性-雷克雅未克（AGES-Reykjavik）研究中检查4137种血清蛋白与AF事件之间的因果关系和预测关系。该研究包括4765名参与者，其中1172名发展为AF。考克斯比例风险回归模型拟合4137基线蛋白质测量调整已知的危险因素。在心血管健康研究（CHS）中对蛋白质相关性进行了重复测试。在双向、双样本孟德尔随机化分析中检查因果关系。在临床风险模型中加入蛋白质水平和AF多基因风险评分（PRS），检查受试者工作特征曲线（AUC）统计量下的时间依赖性面积。AF的蛋白质组特征包括76种蛋白质，其中63种（83%）是新的，29种（38%）在CHS中重复。特征包括N-末端脑利钠肽原（NT-proBNP）依赖性（例如CHST 15、ATP 1B 1和SVEP 1）和独立组分（例如ASPN、AKR 1B和LAMA 1/LAMB 1/LAMC 1）。确定了9个候选因果关系（TAGLN、WARS、CHST 15、CHMP 3、COL 15 A1、DUSP 13、MANBA、QSOX 2和SRL）。反向因果分析表明，大多数AF相关蛋白的遗传易感性AF。N-末端脑钠肽前体改善了事件AF事件的预测接近基线，进一步改善获得的AF-PRS在所有时间点。AF蛋白质组特征包括生物学相关蛋白质，其中一些可能是因果关系。它主要反映了一个NT-proBNP依赖性的遗传易感性AF的后果。N-末端脑钠肽激素原是一个有前途的标记事件AF在短期内，但风险评估纳入PRS可能会改善长期的风险评估。AGES-RS，年龄、基因/环境易感性-雷克雅未克研究; MR，孟德尔随机化; AF，房颤; CHS，心血管健康研究; PRS，多基因风险评分。
Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4137 serum proteins and incident AF in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. The study included 4765 participants, of whom 1172 developed AF. Cox proportional hazards regression models were fitted for 4137 baseline protein measurements adjusting for known risk factors. Protein associations were tested for replication in the Cardiovascular Health Study (CHS). Causal relationships were examined in a bidirectional, two-sample Mendelian randomization analysis. The time-dependent area under the receiver operating characteristic curve (AUC)-statistic was examined as protein levels and an AF-polygenic risk score (PRS) were added to clinical risk models. The proteomic signature of incident AF consisted of 76 proteins, of which 63 (83%) were novel and 29 (38%) were replicated in CHS. The signature included both N-terminal prohormone of brain natriuretic peptide (NT-proBNP)-dependent (e.g. CHST15, ATP1B1, and SVEP1) and independent components (e.g. ASPN, AKR1B, and LAMA1/LAMB1/LAMC1). Nine causal candidates were identified (TAGLN, WARS, CHST15, CHMP3, COL15A1, DUSP13, MANBA, QSOX2, and SRL). The reverse causal analysis suggested that most AF-associated proteins were affected by the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide improved the prediction of incident AF events close to baseline with further improvements gained by the AF-PRS at all time points. The AF proteomic signature includes biologically relevant proteins, some of which may be causal. It mainly reflects an NT-proBNP-dependent consequence of the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide is a promising marker for incident AF in the short term, but risk assessment incorporating a PRS may improve long-term risk assessment. AGES-RS, Age, Gene/Environment Susceptibility-Reykjavik study; MR, Mendelian randomization; AF, atrial fibrillation; CHS, Cardiovascular Health Study; PRS, polygenic risk score.
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影响因子：
37.8
作者：
Huxley RR;Lopez FL;Folsom AR;Agarwal SK;Loehr LR;Soliman EZ;Maclehose R;Konety S;Alonso A
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作者：
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通讯作者：
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