COVID-19 易感性、住院和严重程度与大脑皮质结构的关系：一项孟德尔随机化研究。

COVID-19 susceptibility, hospitalization and severity and the risk of brain cortical structure: a Mendelian randomization study.

机构信息

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

QJM. 2024 Jun 25;117(6):413-421. doi: 10.1093/qjmed/hcad291.

DOI:10.1093/qjmed/hcad291

PMID:38195890

Abstract

BACKGROUND

Observational studies have reported structural changes in the brains of patients with coronavirus disease 2019 (COVID-19); it remains unclear whether these associations are causal.

AIM

We evaluated the causal effects of COVID-19 susceptibility, hospitalization and severity on cortical structures.

DESIGN

Mendelian randomization (MR) study.

METHODS

Data on the different COVID-19 phenotypes were obtained from the latest large-scale genome-wide association study (R7) of the COVID-19 Host Genetics Initiative. Brain structure data, including cortical thickness (TH) and surface area (SA), were obtained from the ENIGMA Consortium. Additionally, we employed the round 5 dataset released in January 2021 as the validation cohort. The inverse-variance weighted (IVW) method was used as the primary analysis in MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. We performed enrichment analysis on the MR analyses that passed the sensitivity analysis filtering.

RESULTS

After IVW and sensitivity analyses, we observed causal associations between COVID-19 susceptibility and rostral middle frontal SAw (P = 0.0308, β = -39.1236), cuneus THw (P = 0.0170, β = -0.0121), medial orbitofrontal THw (P = 0.0002, β = 0.0225), postcentral THw (P = 0.0217, β = -0.0106), temporal pole THw (P = 0.0077, β = 0.0359), medial orbitofrontal SAnw (P = 0.0106, β = -24.0397), medial orbitofrontal THnw (P = 0.0007, β = 0.0232), paracentral SAnw (P = 0.0483, β = -20.1442), rostral middle frontal SAnw (P = 0.0368, β = -81.9719) and temporal pole THnw (P = 0.0429, β = 0.0353). COVID-19 hospitalization had causal effects on medial orbitofrontal THw (P = 0.0053, β = 0.0063), postcentral THw (P = 0.0143, β = -0.0042), entorhinal THnw (P = 0.0142, β = 0.0142), medial orbitofrontal THnw (P = 0.0147, β = 0.0065) and paracentral SAnw (P = 0.0119, β = -7.9970). COVID-19 severity had causal effects on rostral middle frontal SAw (P = 0.0122, β = -11.8296), medial orbitofrontal THw (P = 0.0155, β = 0.0038), superior parietal THw (P = 0.0291, β = -0.0021), lingual SAnw (P = 0.0202, β = -11.5270), medial orbitofrontal THnw (P = 0.0290, β = 0.0039), paracentral SAnw (P = 0.0180, β = -5.7744) and pars triangularis SAnw (P = 0.0151, β = -5.4520).

CONCLUSION

Our MR results demonstrate a causal relationship between different COVID-19 phenotypes and cortical structures.

摘要

背景

观察性研究报告了 2019 年冠状病毒病（COVID-19）患者大脑结构的变化；目前尚不清楚这些关联是否具有因果关系。

目的

我们评估了 COVID-19 易感性、住院和严重程度对皮质结构的因果影响。

设计

孟德尔随机化（MR）研究。

方法

从 COVID-19 宿主遗传学倡议的最新大规模全基因组关联研究（R7）中获取不同 COVID-19 表型的数据。从 ENIGMA 联盟获取大脑结构数据，包括皮质厚度（TH）和皮质表面积（SA）。此外，我们还使用 2021 年 1 月发布的第 5 轮数据集作为验证队列。主要分析方法是逆方差加权（IVW）方法。进行敏感性分析以评估异质性和多效性。对通过敏感性分析筛选的 MR 分析进行富集分析。

结果

经过 IVW 和敏感性分析后，我们观察到 COVID-19 易感性与额中回 SAw（P=0.0308，β=-39.1236）、楔前叶 THw（P=0.0170，β=-0.0121）、内侧眶额皮质 THw（P=0.0002，β=0.0225）、中央后回 THw（P=0.0217，β=-0.0106）、颞极 THw（P=0.0077，β=0.0359）、内侧眶额皮质 SAw（P=0.0106，β=-24.0397）、内侧眶额皮质 THnw（P=0.0007，β=0.0232）、旁中央 SAw（P=0.0483，β=-20.1442）、额中回 SAw（P=0.0368，β=-81.9719）和颞极 THnw（P=0.0429，β=0.0353）之间存在因果关系。COVID-19 住院与内侧眶额皮质 THw（P=0.0053，β=0.0063）、中央后回 THw（P=0.0143，β=-0.0042）、内嗅皮质 THnw（P=0.0142，β=0.0142）、内侧眶额皮质 THnw（P=0.0147，β=0.0065）和旁中央 SAw（P=0.0119，β=-7.9970）之间存在因果关系。COVID-19 严重程度与额中回 SAw（P=0.0122，β=-11.8296）、内侧眶额皮质 THw（P=0.0155，β=0.0038）、上顶叶 THw（P=0.0291，β=-0.0021）、舌回 SAw（P=0.0202，β=-11.5270）、内侧眶额皮质 THnw（P=0.0290，β=0.0039）、旁中央 SAw（P=0.0180，β=-5.7744）和三角部 SAw（P=0.0151，β=-5.4520）之间存在因果关系。