title: Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders.
abstract: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response.
  
  
  
  Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses.
  
  
  
  Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores.
  
  
  
  We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.
authors.forename: Jonathan R I
authors.initials: JR
authors.lastname: Coleman
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|b School of Psychology, University of Sussex , UK.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Lester
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.
authors.forename: Susanna
authors.initials: S
authors.lastname: Roberts
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|c School of Biological and Chemical Sciences, Queen Mary University of London , London , UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Keers
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|d National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust , London, UK.
authors.forename: Sang Hyuck
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|d National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust , London, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: De Jong
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|d National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust , London, UK.
authors.forename: Héléna
authors.initials: H
authors.lastname: Gaspar
authors.affiliation: e Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum , Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Teismann
authors.affiliation: e Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum , Germany.|f Dental Clinic Bochum , Bochum , Germany.
authors.forename: André
authors.initials: A
authors.lastname: Wannemüller
authors.affiliation: e Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum , Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schneider
authors.affiliation: f Dental Clinic Bochum , Bochum , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jöhren
authors.affiliation: e Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum , Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Margraf
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|d National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust , London, UK.
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.affiliation: a King's College London, Institute of Psychiatry, Psychology and Neuroscience, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre , London , UK.|d National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust , London, UK.
authors.forename: Thalia C
authors.initials: TC
authors.lastname: Eley
mesh_terms: D000328:Adult; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D007171:Implosive Therapy / Q000379:methods*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000235:genetics* / Q000628:therapy*; D010641:Phenotype; D010698:Phobic Disorders / Q000235:genetics* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers
keywords: Genetics; anxiety disorders; exposure therapy; gene expression; psychotherapy