Ahdistuneisuushäiriöiden ja unifenotyyppien jaettu geneettinen arkkitehtuuri

Anxiety and sleep disorders frequently co-occur, but most genetic studies have examined anxiety as a broad phenotype, leaving unclear whether putative shared genetic liability with sleep disturbance differs between specific anxiety disorders. This thesis aimed to investigate the shared and disorder-specific genetic architecture of four anxiety phenotypes and nine sleep phenotypes using data from the FinnGen study, with a focus on clinically defined, registry-based phenotypes. Genome-wide association studies (GWAS) were performed to identify phenotype-specific associated loci, genetic correlations were estimated using linkage disequilibrium score regression to quantify shared genome-wide liability, and functional mapping and annotation were used to map associated variants to genes and biological processes. Genetic correlation analyses showed widespread positive correlations between anxiety disorders and sleep phenotypes. Among the specific anxiety disorders, the highest correlation was observed between generalised anxiety disorder and insomnia (rg = 0.74). Overall, the highest and most consistent correlations were observed for insomnia-related phenotypes, including insomnia, Z-medication use, and combined insomnia or Z-medication use. Generalised anxiety disorder and panic disorder showed the most consistent overlap with insomnia-related phenotypes, whereas correlations involving social anxiety disorder were generally weaker. GWAS and functional annotation analyses identified biologically plausible loci and regulatory processes related to neuronal signalling, chromatin organisation, and insomnia-related phenotypes. Functional annotation further supported convergence between anxiety and insomnia-related phenotypes at the level of mapped genes, with 103 mapped genes shared between at least one anxiety phenotype and one sleep phenotype. Five significantly enriched gene sets were shared across broad anxiety and insomnia-related phenotypes, with enriched processes mainly related to chromatin organisation and gene regulation. These findings suggest that anxiety-sleep genetic overlap is not uniform across anxiety disorders and sleep phenotypes, and is strongest for insomnia-related sleep disturbance. Although insomnia-related phenotypes showed the most consistent overlap across anxiety disorders, the pattern was not identical across disorders. This may reflect shared arousal-, stress-, and regulatory mechanisms alongside partly distinct anxiety-specific profiles. Overall, this study underscores the relevance of insomnia-related symptoms in anxiety disorders and suggests that recognising this shared genetic liability could support more integrated assessment and treatment of anxiety and sleep problems.