A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Major depressive disorder (MDD) and anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg≈1). Cognitive behavioural therapy (CBT) is a leading evidence-based treatment, but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy of: adults with anxiety disorders (n=972), adults with major depressive disorder (n=832) and children with anxiety disorders (n=920; meta-analysis n=2,724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms (SNPs) were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits