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.
© 2016 The Royal College of Psychiatrists. 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 semistructured 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.