Shared genetic background and bidirectional risks between anxiety disorders and general medical conditions

Anxiety disorders frequently co-occur with general medical conditions; however, the extent, directionality, and shared genetic risks of these associations remain unclear. This lecture will describe a study that used FinnGen, comprising over 500,000 participants, to systematically examine epidemiological and genetic associations between anxiety disorders and 11 broad ICD-10 categories, as well as 44 individual common general medical conditions. Cox proportional hazard models and genetic analyses were employed. The results demonstrate bidirectional associations between anxiety disorders and most broad medical categories, with the strongest associations observed for gastrointestinal and neurological diseases. Prior gastrointestinal disease (HR [CI 95%] = 2.02 [1.97-2.08]) and neurological disease (HR [CI 95%] = 1.96 [1.91-2.01]) were strong predictors of subsequent anxiety disorders. Conversely, a prior anxiety disorder predicted later gastrointestinal (HR [CI 95%] = 1.77 [1.73-1.82]) and neurological diagnoses (HR [CI 95%] = 1.72 [1.68-1.76]). These associations were mirrored by substantial shared genetic risk (rg = 0.41-0.71, P < 2 × 10^-5) between anxiety disorders and certain gastrointestinal diseases, primarily involving variants in regulatory regions and genes associated with brain function. These findings indicate shared underlying mechanisms between specific medical conditions and anxiety disorders. Genes implicated in both anxiety and gastrointestinal diseases provide a foundation for functional studies to elucidate molecular and cellular mechanisms. The pronounced bidirectional risks highlight potential targets for secondary prevention and treatment in patients with anxiety disorders.