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