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

Jonathan R I Coleman, Kathryn J Lester, Robert Keers, Susanna Roberts, Charles Curtis, Kristian Arendt, Susan Bögels, Peter Cooper, Cathy Creswell, Tim Dalgleish, Catharina A Hartman, Einar R Heiervang, Katrin Hötzel, Jennifer L. Hudson, Tina In-Albon, Kristen Lavallee, Heidi J Lyneham, Carla E Marin, Richard Meiser-Stedman, Talia MorrisMaaike H. Nauta, Ronald M Rapee, Silvia Schneider, Sophie C Schneider, Wendy K Silverman, Mikael Thastum, Kerstin Thirlwall, Polly Waite, Gro Janne Wergeland, Gerome Breen, Thalia C 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: To perform the 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, on completion of treatment (post-treatment), and 3 to 12 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 6-month follow-up. Results: No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-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
Pages (from-to)236-243
JournalThe British Journal of Psychiatry
Volume209
Issue number3
DOIs
Publication statusPublished - Sep 2016

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