文献类型：期刊文献

英文题名：Causality of genetically proxied immunophenotypes on cardiovascular diseases: a Mendelian randomization study

作者：Wang, Xuehan[1];Cheng, Huixin[1];Feng, Meng[2];Jiang, Bing[3];Ren, Chunzhen[3];Chen, Qilin[3];Zhi, Xiaodong[3];Li, Yingdong[1,3]

第一作者：Wang, Xuehan

通信作者：Li, YD[1];Li, YD[2]

机构：[1]Lanzhou Univ, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[2]Shandong Univ, Dept Emergency Med, Qilu Hosp, Jinan, Shandong, Peoples R China;[3]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：15

外文期刊名：FRONTIERS IN IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-85196056140);WOS:【SCI-EXPANDED(收录号:WOS:001248481500001)】；

基金：We thank the AFGen Consortium, HERMES Consortium, CARDIoGRAMplusC4D and UK Biobank, MEGASTROKE Consortium, FinnGen and the original research on immune cells for sharing the GWAS data.r The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Major science and technology projects of Gansu Province (grant numbers 20ZD7FA002); Gansu Province Chinese medicine prevention and treatment of major diseases (grant numbers GZKZD-2018-02); Gansu Education Jiebang Guashuai Project (grant numbers 2021jyjbgs-03).

语种：英文

外文关键词：immunity; cardiovascular diseases; causality; Mendelian randomization; genome-wide association study

摘要：Background Cardiovascular diseases (CVDs) stand as the foremost global cause of mortality, prompting a growing interest in using the potential of immune cells for heart injury treatment. This study aims to assess the causal association between immune cells and CVDs.Methods A total of 731 immune cells were derived from a previously published genome-wide association study (GWAS), which included approximately 22 million genetic variants among 3,757 individuals of Sardinian ancestry. Genetic associations with atrial fibrillation (AF), heart failure, coronary artery disease, myocardial infarction and stroke were extracted from large-scale GWAS. A two-sample Mendelian randomization (MR) analysis was used to assess the causal association between immune cells and CVDs. Replication MR analysis based on FinnGen dataset and meta-analysis are sequentially conducted to validate causal relationships.Results Collectively, genetically predicted 4 immune cell traits were associated with AF and 5 immune cell traits were associated with stroke. Increased levels of IgD- CD38dim absolute count were associated with a higher susceptibility to AF, while increased expression of CD14+ CD16+ monocytes, CD62L on CD62L+ myeloid dendritic cells, and CD16 on CD14- CD16+ monocytes were linked to a decreased susceptibility to AF. Additionally, an elevated susceptibility to stroke was linked to an increase in the percentage of CD39+ resting Tregs and heightened CD27 expression on IgD- CD38+ cells. Conversely, a decreased susceptibility to stroke was associated with increased CD40 expression on monocytes, particularly on CD14+ CD16+ and CD14+ CD16- monocytes, with the latter two showing the most compelling evidence.Conclusion This study identified several immune cell traits that have a causal relationship with CVDs, thus confirming that immune cells play an important role in the pathogenesis of these diseases.