Shared genetics and causal associations between COVID-19 and multiple sclerosis.

ABSTRACT

Neuroinflammation caused by COVID-19 negatively impacts brain metabolism and function, while pre-existing brain pathology may contribute to individuals' vulnerability to the adverse consequences of COVID-19. We used summary statistics from genome-wide association studies (GWAS) to perform Mendelian randomization (MR) analyses, thus assessing potential associations between multiple sclerosis (MS) and two COVID-19 outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and COVID-19 hospitalization). Genome-wide risk genes were compared between the GWAS datasets on hospitalized COVID-19 and MS. Literature-based analysis was conducted to construct molecular pathways connecting MS and COVID-19. We found that genetic liability to MS confers a causal effect on hospitalized COVID-19 (odd ratio [OR] 1.09, 95% confidence interval 1.03-1.16) but not on SARS-CoV-2 infection (1.03, 1.00-1.05). Genetic liability to hospitalized COVID-19 confers a causal effect on MS (1.15, 1.02-1.30). Hospitalized COVID-19 and MS share five risk genes within two loci, including TNFAIP8, HSD17B4, CDC37, PDE4A, and KEAP1. Pathway analysis identified a panel of immunity-related genes that may mediate the links between MS and COVID-19. Our study suggests that MS was associated with a 9% increased risk for COVID-19 hospitalization, while hospitalized COVID-19 was associated with a 15% increased risk for MS. Immunity-related pathways may underlie the link between MS on COVID-19.