Browsing by Author "Tasanko, Elisa"

Objective: Anxiety disorders are a worldwide burden, but the genetic factors predisposing to anxiety disorders are not known. This genome-wide association analysis (GWAS) of anxiety disorders aims to discover both disorder-specific and shared genetic associations between multiple anxiety disorders. More significant associations were expected to be observed with the composite phenotypes than with disorder-specific phenotypes. There are sex-differences in the prevalence of anxiety disorders, so genomic associations were also expected to differ between sexes. Methods: Anxiety disorder diagnoses were searched from the FinnGen data (https://www.finngen.fi/en) to create five groups of cases with broad (N = 24,662), core (N = 7671), phobic (N = 2296) and generalized (N = 2686) anxiety disorders, and panic disorders (N = 3549). In the case groups, 26 – 32 % were males. Controls were the participants without psychiatric diagnoses (N ~ 161,000). All GWASs were also conducted as a sex-stratified analysis. GWASs were conducted with a SAIGE v0.20 -pipeline with age, biological sex, 10 principal components, and genotyping batches as covariates. Results: Several loci associated significantly with multiple anxiety disorders and with specific anxiety disorders. The most significant association was between SORCS3 variants and panic disorder. The SORCS3 variants were also associated with males with panic disorder and core anxiety disorders. Conclusions: The GWAS of the broad anxiety resulted in less significant associations than was hypothesized. SORCS3 has previously been associated with multiple psychiatric phenotypes, but not with panic disorder. As hypothesized, different genetic associations were observed between the sexes. The effect sizes of associations observed were modest, which emphasizes how anxiety disorders develop from an interaction of multiple genetic and environmental risk factors.