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

Br J Psychiatry. 2016 Sep;209(3):236-43. doi: 10.1192/bjp.bp.115.168229. Epub 2016 Mar 17.


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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / therapy
  • Child
  • Child, Preschool
  • Cognitive Behavioral Therapy*
  • Female
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Treatment Outcome