Bidirectional Association and Genetic Background of Anxiety Disorders and General Medical Conditions

ImportanceAnxiety disorders are often comorbid with general medical conditions, but the extent and directionality of these associations and shared genetic risk factors are not well understood. ObjectiveTo investigate the potential associations and the directionality between anxiety disorders and general medical conditions, and to explore the underlying shared genetic risk. DesignWe used FinnGen data since the beginning of the registries or in Cox regression analyses between 2011 and 2022. SettingThe longitudinal FinnGen study combines electronic health record and genomic data. ParticipantsOver 500,000 FinnGen participants. ExposuresAnxiety disorders and general medical conditions were defined based on the International Classification of Diseases codes. Anxiety disorders included panic disorder, generalized anxiety disorder, and phobias. Main Outcomes and MeasuresWe conducted Cox proportional hazard analyses to examine associations between anxiety disorders and 11 general medical condition broad categories. Linkage disequilibrium score regression was used to assess shared genetic risk and two-sample Mendelian randomization to estimate causality using publicly available genome-wide association study summary statistics alongside FinnGen data. ResultsWe observed bidirectional associations between anxiety disorders and most general medical conditions. Gastrointestinal and neurological diseases showed a particularly strong bidirectional association. Prior gastrointestinal (HR [CI 95%] = 2.02 [1.97-2.08]) and neurological (HR [CI 95%] = 1.96 [1.91-2.01]) diseases strongly predicted subsequent anxiety disorders. Conversely, a prior anxiety disorder diagnosis predicted later gastrointestinal (HR [CI 95%] = 1.77 [1.73-1.82]) and neurological (HR [CI 95%] = 1.72 [1.68-1.76]) diagnosis. We found shared genetic risk (P < 2x10-5), notably between anxiety disorders and several gastrointestinal diseases (rg = 0.41-0.71). Pleiotropy analysis highlighted regulatory regions in the genome as the main shared feature between anxiety disorders and gastrointestinal diseases as well as genes linked to brain function. Mendelian randomization suggested a causal association from anxiety disorders to asthma and gastrointestinal diseases, but not vice versa. Conclusions and RelevanceThe bidirectional association and shared genetic risk between anxiety disorders and general medical conditions suggest shared underlying pathophysiological mechanisms. The observed links, particularly the causal association from anxiety to certain medical conditions, emphasize the importance of considering somatic health in psychiatric care and vice versa.