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

Christopher David Rayner, Jonathan Richard Iain Coleman, Kirstin Purves, John Hodsoll, Kimberley Goldsmith, Charles John Curtis, Sang Hyuck Lee, Georg W Alpers, Andersson Evelyn, Volker Arolt, Julia Boberg, Susan Bogels, Cathy Creswell, Peter Cooper, Juergen Deckert, Katharina Domschke, Samir El Alaoui, Lydia Fehm, Anja Growcholewski, Kurt HahlwegAlfons Hamm, Erik Hedman, Einar Heiervang, Jennifer Hudson, Peter Johren, Robert Keers, Tilo Kircher, Thomas Lang, Catharina Lavebratt, Kathryn Lester, Nils Lindefors, Jürgen Margraf, Maaike Nauta, Christiane Pane-Farre, Paul Pauli, Andreas Reif, Ronald M. Rapee, Susanna Louise Roberts, Martin Schalling, Silvia Schneider, Wendy K. Silverman, Andreas Ströhle, Tobias Teismann, Mikael Thastum, André Wannemüller, Heike Weber, Christiane Wolf, Christian Ruck, Gerome Daniel Breen, Thalia Catherine Eley

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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.
Original languageEnglish
Article number150
Number of pages13
JournalTranslational psychiatry
Issue number1
Early online date23 May 2019
Publication statusPublished - 1 Dec 2019


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