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
Number of pages8
JournalThe British Journal of Psychiatry
Volume209
Issue number3
DOIs
Publication statusPublished - Sep 2016

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