Ankylosing spondylitis may increase the risk of mental disorders: a two-sample Mendelian randomization study

Abstract:

Objective To investigate the possible causal link between ankylosing spondylitis（AS） and mental disorders through a two-sample Mendelian randomization（MR） analysis，and to offer genetic insights into the early prevention of the development and progression of mental disorders in patients with AS.Methods Using the public data from non-overlapping genome-wide association studies，AS was considered as the exposure variable，and mental disorders （bipolar affective disorder and major depression，anorexia nervosa，Alzheimer’s disease，and anxiety disorder） as the outcome variables. We used inverse variance weighting（IVW） as the main analysis to assess the causal effect，with the MR-Egger method，weighted median method，weighted mode，and simple mode for supplementary causal analyses. The Cochran’s Q test and MR-Egger intercept test were used for sensitivity analysis.Results The IVW results revealed that genetically predicted AS had positive causal associations with bipolar affective disorder and major depression（odds ratio ［OR］=1.055，95%CI=1.019-1.093，P=0.003） and anorexia nervosa（OR=1.370，95%CI=1.068-1.759，P=0.013） and a negative causal association with Alzheimer’s disease（OR=0.976，95%CI=0.955-0.997，P=0.029），but with no causal association with anxiety disorder（OR=1.034，95%CI=0.906-1.179，P=0.620）. The sensitivity analysis detected no heterogeneity or horizontal pleiotropy（P>0.05），which indicated no bias in the results. The leave-one-out analysis suggested that the results were robust.Conclusion This study provides new evidence for causal relationships between AS and mental disorders. AS may increase the risk of bipolar affective disorder and major depression and anorexia nervosa. These findings offer new insights into the genetic research of mental disorders. However，the conclusions need further MR-based validation with larger-sample genome-wide association data.