Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders.
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Br J Psychiatry
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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.
AuthorsColeman, JRI; Lester, KJ; Keers, R; Roberts, S; Curtis, C; Arendt, K; Bögels, S; Cooper, P; Creswell, C; Dalgleish, T; Hartman, CA; Heiervang, ER; Hötzel, K; Hudson, JL; In-Albon, T; Lavallee, K; Lyneham, HJ; Marin, CE; Meiser-Stedman, R; Morris, T; Nauta, MH; Rapee, RM; Schneider, S; Schneider, SC; Silverman, WK; Thastum, M; Thirlwall, K; Waite, P; Wergeland, GJ; Breen, G; Eley, TC
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