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

Abstract

BackgroundAnxiety 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.AimsTo perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).MethodPresence 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.ResultsNo 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.ConclusionsThis 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.

A Longitudinal Twin and Sibling Study of Associations between Insomnia and Depression Symptoms in Young Adults

“…As with any area of psychiatric genetics, the work requires large sample sizes and most studies to date have been underpowered (e.g., work on pediatric anxiety 48 ). However there are preliminary indications that there are genetic influences on response to psychological treatment, 49 indicating that this is a fruitful avenue for further research. Future work by our group will examine genetic prediction of response to CBT for insomnia symptoms and whether improving those symptoms has positive effects on depression symptoms.…”

A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders

“…Genotyping and quality control procedures for the GxT study are documented elsewhere [36]. In brief, DNA was extracted from buccal swabs and saliva and genotyped on Illumina Human Core Exome-12v1.0 microarrays.…”

Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders

“…DNA from saliva samples was extracted using Prep‐it.L2P according to the manufacturers protocol (DNA Genotek). Sample preparation prior to genotyping is described elsewhere [Coleman et al, ]. In brief, samples were subjected to ultrafiltration and resuspension to increase DNA concentration and included in genotyping if the resulting concentration exceeded 50 ng/ul.…”

“…Quality control and imputation procedures for those samples with microarray data are provided in full elsewhere [Coleman et al, ]. Briefly, common variants (minor allele frequency >5%) were included in the analyses if they were genotyped in >99% of samples and if they did not deviate substantially from Hardy–Weinberg equilibrium (HWE test P ‐value > 10 −5 ).…”