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哮喘的遗传易感性与心血管疾病风险:一项孟德尔随机化研究。

Genetic liability to asthma and risk of cardiovascular diseases: A Mendelian randomization study.

作者信息

Chen Heng, Chen Wei, Zheng Liangrong

机构信息

Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Department of Respiratory and Critical Care Medicine, Ruian People's Hospital, Wenzhou, China.

出版信息

Front Genet. 2022 Jul 26;13:879468. doi: 10.3389/fgene.2022.879468. eCollection 2022.

Abstract

Epidemiological studies have suggested positive associations between asthma and the risk of cardiovascular diseases (CVDs). However, causality remains inconclusive. We aim to explore the causal associations between asthma and CVDs risk using the Mendelian Randomization (MR) approach. We obtained summary-level data for eight CVDs [including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), stroke, ischemic stroke, large artery stroke, small vessel stroke, and cardioembolic stroke] from several large genome-wide association studies (GWASs) and the FinnGen consortium. Nine lead single-nucleotide polymorphisms associated with asthma ( < 5 × 10) were identified from the GWAS conducted by the Trans-National Asthma Genetic Consortium. MR analyses were performed using the inverse variance weighted method, supplemented by the weighted median and MR-Egger methods. Inverse variance weighted method showed suggestive effects of genetically determined asthma on AF (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02, 1.14; = 0.009) and HF (OR, 1.05; 95% CI, 1.01, 1.09; = 0.029). We found no causal associations between asthma and other CVDs. No horizontal pleiotropy was observed. This MR study provides genetic evidence suggesting a causal association between asthma and the risk of AF and HF, although not at the level of significance after multiple testing correction. Programs aimed at treating asthma among asthmatics might help prevent the adverse health effects inflicted by CVDs.

摘要

流行病学研究表明哮喘与心血管疾病(CVD)风险之间存在正相关。然而,因果关系仍不明确。我们旨在使用孟德尔随机化(MR)方法探索哮喘与CVD风险之间的因果关联。我们从几项大型全基因组关联研究(GWAS)和芬兰基因组联盟获得了八种CVD的汇总数据[包括心房颤动(AF)、冠状动脉疾病(CAD)、心力衰竭(HF)、中风、缺血性中风、大动脉中风、小血管中风和心源性栓塞性中风]。从跨国哮喘遗传联盟进行的GWAS中鉴定出九个与哮喘相关的主要单核苷酸多态性(<5×10)。使用逆方差加权法进行MR分析,并辅以加权中位数和MR-Egger方法。逆方差加权法显示基因决定的哮喘对AF(优势比(OR),1.08;95%置信区间(CI),1.02,1.14;P = 0.009)和HF(OR,1.05;95%CI,1.01,1.09;P = 0.029)有提示性影响。我们未发现哮喘与其他CVD之间存在因果关联。未观察到水平多效性。这项MR研究提供了遗传证据,表明哮喘与AF和HF风险之间存在因果关联,尽管在多重检验校正后未达到显著水平。针对哮喘患者治疗哮喘的项目可能有助于预防CVD造成的不良健康影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1472/9360591/9be1ccd10f62/fgene-13-879468-g001.jpg

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