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COVID-19 susceptibility, hospitalization and severity and the risk of brain cortical structure: a Mendelian
1Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Insights
This study used Mendelian randomization to investigate causal links between COVID-19 and brain structure. Findings reveal significant associations between COVID-19 susceptibility, hospitalization, severity, and alterations in cortical thickness and surface area.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Observational studies suggest structural brain changes in COVID-19 patients.
- Causal links between COVID-19 and brain alterations remain unclear.
Purpose of the Study:
- To evaluate the causal effects of COVID-19 susceptibility, hospitalization, and severity on cortical structures.
- To investigate the impact of COVID-19 on brain morphology using genetic data.
Main Methods:
- A Mendelian randomization (MR) study design was employed.
- Utilized large-scale genome-wide association study data for COVID-19 phenotypes and brain structure data (cortical thickness and surface area) from the ENIGMA Consortium.
- Inverse-variance weighted (IVW) method with sensitivity analyses for robustness.
Main Results:
- Causal associations were found between COVID-19 susceptibility and specific cortical areas (e.g., rostral middle frontal, cuneus, medial orbitofrontal).
- COVID-19 hospitalization showed causal effects on medial orbitofrontal and postcentral cortical structures.
- COVID-19 severity was causally linked to changes in rostral middle frontal, medial orbitofrontal, and other cortical regions.
Conclusions:
- The study demonstrates a causal relationship between various COVID-19 phenotypes and alterations in cortical structures.
- Results highlight the impact of COVID-19 on brain morphology, supporting further research into neurological consequences.
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.
