Ankylosing spondylitis and psychiatric disorders in European population: a Mendelian randomization study

Epidemiologic evidence has demonstrated a correlation between ankylosing spondylitis and psychiatric disorders. However, little is known about the common genetics and causality of this association. This study aimed to investigate the common genetics and causality between ankylosing spondylitis (AS) and psychiatric disorders.

A two-sample Mendelian Randomization (MR) analysis was carried out to confirm causal relationships between ankylosing spondylitis and five mental health conditions including major depressive disorder (MDD), anxiety disorder (AXD), schizophrenia (SCZ), bipolar disorder (BIP), and anorexia nervosa (AN). Genetic instrumental variables associated with exposures and outcomes were derived from the largest available summary statistics of genome-wide association studies (GWAS). Bidirectional causal estimation of MR was primarily obtained using the inverse variance weighting (IVW) method. Other MR methods include MR-Egger regression, Weighted Median Estimator (WME), Weighted Mode, Simple Mode, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses are conducted to estimate the robustness of MR results.

The findings suggest that AS may be causally responsible for the risk of developing SCZ (OR = 1.18, 95% confidence interval = (1.06, 1.31), P = 2.58 × 10^-3) and AN (OR = 1.32, 95% confidence interval = (1.07, 1.64), P = 9.43 × 10^-3). In addition, MDD, AXD, SCZ, AN, and BIP were not inversely causally related to AS (all p > 0.05).

Our study provides fresh insights into the relationship between AS and psychiatric disorders (SCZ and AN). Furthermore, it may provide new clues for risk management and preventive interventions for mental disorders in patients with AS.