Asthma causally affects the brain cortical structure: a Mendelian randomization study.

IF 1.3 4区 医学 Q3 ALLERGY
Journal of Asthma Pub Date : 2025-09-01 Epub Date: 2025-04-23 DOI:10.1080/02770903.2025.2493123
Tingting Fu, Xiao Fu, Jing Gao, Shilong Zhao, Chunling Hu, Junlu Li, Lihua Xing
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引用次数: 0

Abstract

Objective: The potential causal relationship between asthma and brain structures remains uncertain. We performed a two-sample Mendelian randomization to investigate the causal effects of various asthma phenotypes - unspecified asthma, moderate-to-severe asthma, childhood-onset asthma, and adult-onset asthma (AOA) - on cerebral cortex structure.

Methods: We utilized phenotype data derived from genome-wide association studies (GWASs). The ENIGMA Consortium GWAS provided outcome variables for surface area (SA) and thickness across the whole brain and 34 region-specific areas of the cerebral cortex. Using the inverse variance-weighted method as our primary estimation approach, we employed several techniques, including Cochran's Q statistic, the MR-PRESSO global test, MR-Egger, and weighted median, to assess heterogeneity and pleiotropy, thereby ensuring the robustness of our findings. Additionally, we conducted enrichment analyses of gene sets with causal effects on cortical structure and applied bioinformatics techniques to construct interaction networks and identify hub nodes.

Results: At the global level, AOA was associated with a significant reduction in full cortical SA (β = -58.49 mm2, p = 0.017). In regional analyses, moderate-to-severe asthma exhibited a more pronounced impact on the cerebral cortex compared to other phenotypes. Enrichment analysis revealed that pathways implicated in brain morphology among asthma patients were primarily linked to immune and inflammation-driven pathways.

Conclusions: Our findings provide new evidence supporting a causal relationship between asthma and alterations in cortical structure, offering potential explanations for cognitive and psychiatric impairments observed in individual post-asthma.

哮喘会影响大脑皮质结构:孟德尔随机研究。
目的:哮喘与脑结构之间的潜在因果关系尚不确定。我们进行了双样本孟德尔随机化,以调查各种哮喘表型(未指明哮喘、中重度哮喘、儿童期哮喘和成年期哮喘)对大脑皮层结构的因果影响。方法:我们利用来自全基因组关联研究(GWASs)的表型数据。ENIGMA联盟GWAS提供了整个大脑和大脑皮层34个区域特定区域的表面积(SA)和厚度的结果变量。我们使用反方差加权法作为我们的主要估计方法,采用了几种技术,包括科克伦Q统计量、MR-PRESSO全局检验、MR-Egger和加权中位数,来评估异质性和多效性,从而确保我们研究结果的稳健性。此外,我们还进行了对皮质结构有因果影响的基因集的富集分析,并应用生物信息学技术构建相互作用网络和识别枢纽节点。结果:在整体水平上,AOA与全皮质SA显著降低相关(β = -58.49 mm2, p = 0.017)。在区域分析中,与其他表型相比,中度至重度哮喘对大脑皮层的影响更为明显。富集分析显示,哮喘患者脑形态学相关通路主要与免疫和炎症驱动通路相关。结论:我们的研究结果提供了新的证据,支持哮喘和皮质结构改变之间的因果关系,为个体哮喘后观察到的认知和精神障碍提供了潜在的解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Asthma
Journal of Asthma 医学-过敏
CiteScore
4.00
自引率
5.30%
发文量
158
审稿时长
3-8 weeks
期刊介绍: Providing an authoritative open forum on asthma and related conditions, Journal of Asthma publishes clinical research around such topics as asthma management, critical and long-term care, preventative measures, environmental counselling, and patient education.
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