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

  • Jonathan R. I. Coleman (a1), Kathryn J. Lester (a2), Robert Keers (a3), Susanna Roberts (a3), Charles Curtis (a4), Kristian Arendt (a5), Susan Bögels (a6), Peter Cooper (a7), Cathy Creswell (a8), Tim Dalgleish (a9), Catharina A. Hartman (a10), Einar R. Heiervang (a11), Katrin Hötzel (a12), Jennifer L. Hudson (a13), Tina In-Albon (a14), Kristen Lavallee (a15), Heidi J. Lyneham (a13), Carla E. Marin (a16), Richard Meiser-Stedman (a9), Talia Morris (a13), Maaike H. Nauta (a17), Ronald M. Rapee (a13), Silvia Schneider (a12), Sophie C. Schneider (a13), Wendy K. Silverman (a16), Mikael Thastum (a5), Kerstin Thirlwall (a8), Polly Waite (a8), Gro Janne Wergeland (a18), Gerome Breen (a4) and Thalia C. Eley (a3)...
Abstract
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.

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Copyright
Corresponding author
Professor Thalia Eley, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience – PO80, DeCrespigny Park, Denmark Hill, London SE5 8AF, UK. Email: thalia.eley@kcl.ac.uk)
Footnotes
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These authors contributed equally to the work

Declaration of interest

R.M.R., J.L.H. and H.J.L. are co-authors of the Cool Kids program but receive no direct payments. C. Creswell is co-author of books in the ‘Overcoming’ series and receives royalties. W.K.S. is author of the Anxiety Disorders Interview Schedule for Children and receives royalties. G.B. is a consultant in pre-clinical genetics for Eli Lilly.

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

  • Jonathan R. I. Coleman (a1), Kathryn J. Lester (a2), Robert Keers (a3), Susanna Roberts (a3), Charles Curtis (a4), Kristian Arendt (a5), Susan Bögels (a6), Peter Cooper (a7), Cathy Creswell (a8), Tim Dalgleish (a9), Catharina A. Hartman (a10), Einar R. Heiervang (a11), Katrin Hötzel (a12), Jennifer L. Hudson (a13), Tina In-Albon (a14), Kristen Lavallee (a15), Heidi J. Lyneham (a13), Carla E. Marin (a16), Richard Meiser-Stedman (a9), Talia Morris (a13), Maaike H. Nauta (a17), Ronald M. Rapee (a13), Silvia Schneider (a12), Sophie C. Schneider (a13), Wendy K. Silverman (a16), Mikael Thastum (a5), Kerstin Thirlwall (a8), Polly Waite (a8), Gro Janne Wergeland (a18), Gerome Breen (a4) and Thalia C. Eley (a3)...
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