Mendelian Randomization Analyses Accounting for Causal Effect of COVID-19 on Brain Imaging-Derived Phenotypes

Article type: Research Article

Authors: Lu, Jiajie^{a; c} | Huang, Rihong^{a; c} | Peng, Yuecheng^{a; c} | Zhang, Jinming^b | Liang, Kairong^a | Wang, Yezhong^{a; *} | Feng, Yi^{d; e; *} | Wang, Zhaotao^{a; c; *}

Affiliations: [a] Institute of Neuroscience, Department of Neurosurgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China | [b] Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China | [c] Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China | [d] Department of Thoracic Surgery and Oncology, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China | [e] Guangzhou Institute of Respiratory Health, Guangzhou, China

Correspondence: [*] Correspondence to: Zhaotao Wang, MD, PhD, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Tel.: +8618024096526; E-mail: [email protected] and Yezhong Wang, MD, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Tel.: +8613902237122; E-mail: [email protected] and Yi Feng, MD, Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Tel.: +86 20 83337792; E-mail: [email protected].

Abstract: Background:The coronavirus disease 2019 (COVID-19) has been a major challenge to global health and a financial burden. Little is known regarding the possible causal effects of COVID-19 on the macro- and micro-structures of the human brain. Objective:To determine the causal links between susceptibility, hospitalization, and the severity of COVID-19 and brain imaging-derived phenotypes (IDPs). Methods:Mendelian randomization (MR) analyses were performed to investigate the causal effect of three COVID-19 exposures (SARS-CoV-2 infection, hospitalized COVID-19, and critical COVID-19) on brain structure employing summary datasets of genome-wide association studies. Results:In terms of cortical phenotypes, hospitalization due to COVID-19 was associated with a global decrease in the surface area (SA) of the cortex structure (β= –624.77, 95% CI: –1227.88 to –21.66, p = 0.042). At the regional level, SARS-CoV-2 infection was found to have a nominally causal effect on the thickness (TH) of the postcentral region (β= –0.004, 95% CI: –0.007 to –0.001, p = 0.01), as well as eight other IDPs. Hospitalized COVID-19 has a nominally causal relationship with TH of postcentral (β= –0.004, 95% CI: –0.007 to –0.001, p = 0.01) and other 6 IDPs. The nominally causal effects of critical COVID-19 on TH of medial orbitofrontal (β=0.004, 95% CI: 0.001to 0.007, p = 0.004) and other 7 IDPs were revealed. Conclusions:Our study provides compelling genetic evidence supporting causal relationships between three COVID-19 traits and brain IDPs. This discovery holds promise for enhancing predictions and interventions in brain imaging.

Keywords: Alzheimer’s disease, brain structure, COVID-19, Mendelian randomization

DOI: 10.3233/JAD-230626

Journal: Journal of Alzheimer's Disease, vol. 96, no. 3, pp. 1059-1070, 2023