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

(2016) 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. World Journal of Biological Psychiatry, 18 (3). pp. 215-226. ISSN 1562215-226. ISSN -2975 This version is available from Sussex Research Online: http://sro.sussex.ac.uk/62023/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data-driven and literature-driven manner.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. ResultsExpression levels were not associated with either treatment phenotype in any analysis.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. ConclusionsWe assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.

DNA methylation of FKBP5 and response to exposure‐based psychological therapy

“…Full details of data preparation and quality-control procedures are reported elsewhere (Roberts et al, 2017). In order to control for potential population stratification, the first two principal components ("PC1" and "PC2") from genome-wide genotyping data (details reported elsewhere; Coleman et al, 2016) were also tested for association with treatment outcome. Probes were then transformed and normalized, and outliers identified and removed.…”

“…The receipt, storage and analysis of samples were approved by the London-Bentham NRES Committee and the King's College London Psychiatry, Nursing and Midwifery Research Ethics Sub-Committee.3 | ANALYSES3.1 | Confounding factorsBaseline severity, age, BMI, gender, smoking status, psychoactive medication status, and other medication status were tested for association with percentage reduction in clinical severity and change in DNA methylation between the time-points tested(Tables 1-3). In order to control for potential population stratification, the first two principal components ("PC1" and "PC2") from genome-wide genotyping data (details reported elsewhere;Coleman et al, 2016) were also tested for association with treatment outcome. Variables displaying a significant association with either treatment outcome or change in DNA methylation (p < .05) were included as covariates in the relevant analyses(Tables 1-3).…”

A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

“…No significant genetic associations with therapy outcome were observed, although three independent loci were of suggestive significance ( P < 5 × 10 −6 ). A second therapy outcome GWAS, which was part of a broader gene expression analysis ( n = 182) also detected several loci that were also of suggestive significance ( P < 5 × 10 −6 ) 41 . Such analyses require large samples to detect small genetic effects at genome-wide significance.…”

Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders

“…Population stratification was tested for association with outcome using the first two principal components from genome-wide genotyping data (‘PC1’, ‘PC2’). 38 Treated diagnosis was not associated with outcome at post treatment ( F =0.44, P =0.644) or at follow-up ( F =0.74, P =0.480).…”

“… 67 To this end, a study from our team showed genotype-dependent changes in FKBP5 DNA methylation associated with treatment outcome. 14 However, in a companion paper to this article combining genome-wide genetic and transcriptomic data (including an extended sample from this cohort 38 ), a number of eQTLs (DNA sequence variation associated with gene expression) were identified, but interactions between genetic variants and treatment response were not significantly associated with expression levels. Nonetheless, future therapygenetics research would benefit from the continued use of genome-wide protocols, and the integration of genetic, epigenetic and transcriptomic information in order to elucidate the potential biological mechanisms underlying psychological treatment response.…”