A major role for common genetic variation in anxiety disorders

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. Selecting from 126,443 individuals in the UK Biobank, we conducted a genome-wide association study of self-reported “Any anxiety... [ view full abstract ]

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. Selecting from 126,443 individuals in the UK Biobank, we conducted a genome-wide association study of self-reported “Any anxiety disorder” (cases n = 21,108). As a secondary phenotype we also defined severe levels of current generalised anxiety symptoms (“Current anxiety symptoms”; cases n = 19,012).

We had three sources of data for replication analyses. First, we identified cases who met criteria for self-rated lifetime assessment of probable generalised anxiety disorder, who were not also identified as meet our “Any anxiety disorder” criteria, thus these definitions were independent of one another (“Probable GAD”; cases n = 4,345). Second, we utilised the published summary statistics from the ANGST consortium (cases n = 3,695). Finally, we analysed anxiety cases defined using the same criteria as for our “Any anxiety disorder” definition from the iPSYCH consortium (cases n = 2,829). Findings from these three sets of participants were considered individually, and were then meta-analysed together to create a combined replication sample. This was then meta-analysed with our “discovery”, the UK Biobank “Any anxiety disorders” cases.

The liability scale common variant heritability estimate for “Any anxiety disorder” was 31.1%, and for the total combined sample meta-analysis was 13.8%. Three novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism.

Genetic correlations between different anxiety definitions and levels of severity both within and across samples were very high.

Anxiety phenotypes also showed significant genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies.

We conclude that common genetic variation underlies a substantive proportion of the genetic architecture underlying anxiety.