银屑病对主动脉瓣狭窄的因果效应:双样本孟德尔随机研究。

IF 1.8 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Ke-Xin Jiang, Yan Wang, Yu-Tong Liu, Yanjiani Xu, Fang-Yang Huang, Mao Chen
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引用次数: 0

摘要

背景:流行病学研究表明,银屑病与主动脉瓣狭窄(AS)风险增加之间存在潜在联系,但银屑病对AS进展的影响仍不确定。本研究旨在利用孟德尔随机分析法(MR)研究银屑病与主动脉瓣狭窄之间的因果关系,并揭示这种关联的潜在机制:方法:利用公开的银屑病和强直性脊柱炎全基因组关联研究(GWAS)的汇总统计数据,进行了双样本 MR 分析。为每个因果单核苷酸多态性(SNPs)确定了顺式-eQTL和重要基因,然后进行了通路富集和蛋白-蛋白相互作用(PPI)分析,以进行功能评估。枢纽基因由 Cytospace 确定。获得了AS群体的转录谱,并利用分子复杂性检测(MCODE)对相互关联的基因网络进行了聚类:结果:我们的研究结果表明,银屑病与强直性脊柱炎之间存在明显的因果关系,银屑病的遗传易感性与较高的强直性脊柱炎风险相关(几率比:1.46)。通路和PPI分析揭示了15个枢纽基因,包括HLA-C、HLA-B、ISG15、IFIT3和MX2,以及连接银屑病和强直性脊柱炎的免疫相关通路。此外,对强直性脊柱炎数据库进行的转录剖析突显了适应性免疫细胞在强直性脊柱炎发病过程中的重要参与。值得注意的是,在15个枢纽基因中,ISG15、MX2、OAS3、OASL、IFI6和EPSTI1在AS人群中的表达量较高:我们的研究提供了令人信服的证据,证明银屑病与强直性脊柱炎之间存在因果关系。结论:我们的研究为银屑病和强直性脊柱炎之间的因果关系提供了令人信服的证据。此外,所发现的枢纽基因和免疫相关通路可能在这两种疾病的发展过程中发挥着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Causal effect of psoriasis on aortic valve stenosis: a two-sample Mendelian randomization study.

Background: Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis (AS), though the impact of psoriasis on AS progression remains uncertain. The study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization (MR) analysis, as well as to uncover potential mechanisms underlying this association.

Methods: A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies (GWAS) of psoriasis and AS. Cis-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms (SNPs), followed by pathway enrichment and protein-protein interaction (PPI) analysis for functional evaluation. Hub genes were pinpointed by Cytospace. The transcriptional profile of AS population was acquired, and interconnected genes networks were clustered using Molecular Complex Detection (MCODE).

Results: Our results demonstrate a significant causal relationship between psoriasis and AS, with a genetic predisposition to psoriasis associated with a higher AS risk (odds ratio: 1.46). Pathway and PPI analyses unveiled 15 hub genes, including HLA-C, HLA-B, ISG15, IFIT3, and MX2, along with immune-related pathways linking psoriasis and AS. Moreover, the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS development. Notably, among the 15 hub genes, ISG15, MX2, OAS3, OASL, IFI6, and EPSTI1 exhibited higher expression in the AS population.

Conclusion: Our study provides compelling evidence supporting a causal relationship between psoriasis and AS. Furthermore, the identified hub genes and immune-related pathways may play an important role in the development of both diseases.

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来源期刊
Journal of Geriatric Cardiology
Journal of Geriatric Cardiology CARDIAC & CARDIOVASCULAR SYSTEMS-GERIATRICS & GERONTOLOGY
CiteScore
3.30
自引率
4.00%
发文量
1161
期刊介绍: JGC focuses on both basic research and clinical practice to the diagnosis and treatment of cardiovascular disease in the aged people, especially those with concomitant disease of other major organ-systems, such as the lungs, the kidneys, liver, central nervous system, gastrointestinal tract or endocrinology, etc.
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