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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.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
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.
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.
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.
We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
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