Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Jonathan Coleman, Kathryn Jane Lester, Robert Keers, Susanna Roberts, Charles John Curtis, Kristian Arendt, Susan Bogels, Peter Cooper, Cathy Creswell, Tim Dalgleish, Catharina Hartman, Einar Heiervang, Katrin Hötzel, Jennifer L. Hudson, Tina In-Albon, Kristen Lavallee, Heidi Lyneham, Carla Marin, Richard Meiser-Stedman, Talia MorrisMaaike Nauta, Ronald M. Rapee, Silvia Schneider, Sophie C. Schneider, Wendy K. Silverman, Mikael Thastum, Kerstin Thirlwall, Polly Waite, Gro Janne Wergeland, Gerome Daniel Breen, Thalia Catherine Eley

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Abstract

Background Anxiety disorders are common, and cognitive behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims Perform first genome-wide association study (GWAS) of psychological treatment response, in children with anxiety disorders (N = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, upon completion of treatment (“post-treatment”), and three to twelve months after treatment completion (“follow-up”). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at six-month follow-up. Results No variants passed a genome-wide significance threshold (p=5x10-8) in either analysis. Four met criteria for suggestive significance (p<5x10-6) in association with response post-treatment, and three in the six-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
Original languageEnglish
JournalBritish Journal of Psychiatry
Volume208
Issue number3
Early online date17 Mar 2016
DOIs
Publication statusE-pub ahead of print - 17 Mar 2016

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