Viral infections and risk of mental illness: A Mendelian randomization study

Prior epidemiological evidence suggests associations between viral infections and psychiatric disorders, yet causal relationships remain insufficiently characterized. This study aims to investigate potential causal links using genetic instrumental variables.

A two-sample Mendelian randomization (MR) analysis was conducted using pooled European-ancestry genomic data. Exposures included hepatitis B virus (HBV), human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human papillomavirus (HPV), and Epstein-Barr virus (EBV) infections. Outcomes encompassed generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), schizophrenia (SCH), major depressive disorder (MDD), and manic episodes. Causal estimates were primarily derived via inverse variance weighting (IVW), with robustness assessed through MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated via Cochran's Qstatistic, MR-Egger intercept, and sensitivity plots.

HBV infection was associated with reduced GAD risk (OR = 0.94; 95 % CI [0.91, 0.97]; P = 0.0012). Similarly, HIV and SARS-CoV-2 infections exhibited protective effects against OCD (OR = 0.84; 95 % CI [0.72, 0.97]; P = 0.019 and OR = 0.78; 95 % CI [0.61, 0.99]; P = 0.039). HPV infection decreased SCH risk (OR = 0.84; 95 % CI [0.76, 0.92]; P = 0.0005). Conversely, EBV infection elevated MDD risk (OR = 1.00; 95 % CI [1.00, 1.01]; P = 0.0015). Sensitivity analyses confirmed minimal pleiotropy (Q > 0.05; MR-Egger intercept P > 0.1).

This MR analysis provides genetic evidence supporting causal roles of specific viral infections in psychiatric disorders. Findings underscore the clinical relevance of viral prevention strategies for mental health outcomes.