The genetic and environmental hierarchical structure of anxiety and depression in the UK Biobank

Background Anxiety and depressive disorders can be classified under a bidimensional model, where depression and generalized anxiety disorder are represented by distress and the other anxiety disorders, by fear. The phenotypic structure of this model has been validated, but twin studies only show partial evidence for genetic and environmental distinctions between distress and fear. Moreover, the effects of genetic variants are mostly shared between anxiety and depression, but the genome-wide genetic distinction between distress and fear remains unexplored. This study aimed to examine the degree of common genetic variation overlap between distress and fear, and their associations with the psychosocial risk factors of loneliness and social isolation. Methods We used genome-wide data from 157,366 individuals in the UK Biobank who answered a mental health questionnaire. Results Genetic correlations indicated that depression and generalized anxiety had a substantial genetic overlap, and that they were genetically partially distinct from fear disorders. Associations with loneliness, but not social isolation, showed that loneliness was more strongly associated with both distress disorders than with fear. Conclusions Our findings shed light on genetic and environmental mechanisms that are common and unique to distress and fear and contribute to current knowledge on individuals' susceptibility to anxiety and depression.