EXPLORING THE GENOME-WIDE GENETIC OVERLAP BETWEEN ANXIETY AND FEAR DISORDERS

ABSTRACT

Background: Twin studies have consistently shown a high genetic overlap amongst anxiety disorders and depression. Some research has also identified modest genetic specificity to fear-based anxiety disorders not shared with general anxiety. Identifying the genetic variants shared amongst all anxiety disorders or specific to one or more requires large sample sizes. Measuring anxiety disorders in large cohorts typically involves in-depth symptom-based diagnoses or minimally phenotyped single-item self-report diagnoses. A trade-off exists between maximising sample size and the level of detail in the phenotyping. Aims: First, to explore genetic correlations between generalised anxiety disorder (GAD) and the fear disorders (panic disorder, agoraphobia, specific phobia and social phobia) using a combination of in-depth and minimal phenotyping. Second, to compare the results from using minimal phenotyping of the anxiety disorders to that of in-depth phenotyping. Methods: We will use two case-only samples for analyses the Genetic Links to Anxiety and Depression (GLAD) Study (∼N = 18,000) and the Australian Genetics of Depression Study (AGDS) (∼18,000). In addition, we will use three studies that provide both cases and controls the COVID-19 Psychiatric and Neurological Genetics (COPING) study (N = ∼10,000), the QSkin study (N = ∼18,000) and the UK Biobank (N = ∼157,366). We will conduct three independent sets of case-control anxiety disorder genome-wide association studies (GWAS) before meta-analysing all five samples together (expected N cases ∼53,000, N controls ∼160,000). Results from GWAS meta-analyses of lifetime anxiety disorder, GAD, and fear-based disorders will be used to explore genetic correlations across anxiety disorders and depression and a wide range of complex traits. As sensitivity analyses, we will explore genetic correlations between anxiety phenotypes assessed using minimally phenotyped single-item diagnoses versus in-depth symptom-based diagnoses. Results: We hypothesise that the anxiety disorders will have a SNP-based heritability of approximately 15%. We also hypothesise that GAD and fear-based disorders will be moderately to highly genetically correlated, with some genetic variants that are specific to the fear disorders [1]. Disclosure Nothing to disclose.