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

TY - JOUR

T1 - Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

AU - Coleman, Jonathan

AU - Lester, Kathryn Jane

AU - Keers, Robert

AU - Roberts, Susanna

AU - Curtis, Charles John

AU - Arendt, Kristian

AU - Bogels, Susan

AU - Cooper, Peter

AU - Creswell, Cathy

AU - Dalgleish, Tim

AU - Hartman, Catharina

AU - Heiervang, Einar

AU - Hötzel, Katrin

AU - Hudson, Jennifer L.

AU - In-Albon, Tina

AU - Lavallee, Kristen

AU - Lyneham, Heidi

AU - Marin, Carla

AU - Meiser-Stedman, Richard

AU - Morris, Talia

AU - Nauta, Maaike

AU - Rapee, Ronald M.

AU - Schneider, Silvia

AU - Schneider, Sophie C.

AU - Silverman, Wendy K.

AU - Thastum, Mikael

AU - Thirlwall, Kerstin

AU - Waite, Polly

AU - Wergeland, Gro Janne

AU - Breen, Gerome Daniel

AU - Eley, Thalia Catherine

PY - 2016/3/17

Y1 - 2016/3/17

N2 - 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 Perform 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, upon completion of treatment (“post-treatment”), and three to twelve 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 six-month follow-up. Results No variants passed a genome-wide significance threshold (p=5x10-8) in either analysis. Four met criteria for suggestive significance (p<5x10-6) in association with response post-treatment, and three in the six-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.

AB - 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 Perform 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, upon completion of treatment (“post-treatment”), and three to twelve 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 six-month follow-up. Results No variants passed a genome-wide significance threshold (p=5x10-8) in either analysis. Four met criteria for suggestive significance (p<5x10-6) in association with response post-treatment, and three in the six-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.

U2 - 10.1192/bjp.bp.115.168229

DO - 10.1192/bjp.bp.115.168229

M3 - Article

SN - 0007-1250

VL - 208

JO - British Journal of Psychiatry

JF - British Journal of Psychiatry

IS - 3

ER -