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Significance of risk polymorphisms for depression depends on stress exposure

Gonda, Xénia and Hullam, Gabor and Antal, Péter and Eszlari, Nora and Petschner, Péter and Hökfelt, T. G. and Anderson, I. M. and Deakin, J. F. and Juhász, Gabriella and Bagdy, György (2018) Significance of risk polymorphisms for depression depends on stress exposure. SCIENTIFIC REPORTS, 8 (1). p. 3946. ISSN 2045-2322

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Abstract

Depression is a polygenic and multifactorial disorder where environmental effects exert a significant impact, yet most genetic studies do not consider the effect of stressors which may be one reason for the lack of replicable results in candidate gene studies, GWAS and between human studies and animal models. Relevance of functional polymorphisms in seven candidate genes previously implicated in animal and human studies on a depression-related phenotype given various recent stress exposure levels was assessed with Bayesian relevance analysis in 1682 subjects. This Bayesian analysis indicated a gene-environment interaction whose significance was also tested with a traditional multivariate analysis using general linear models. The investigated genetic factors were only relevant in the moderate and/or high stress exposure groups. Rank order of genes was GALR2 > BDNF > P2RX7 > HTR1A > SLC6A4 > CB1 > HTR2A, with strong relevance for the first four. Robust gene-gene-environment interaction was found between BDNF and HTR1A. Gene-environment interaction effect was confirmed, namely no main effect of genes, but a significant modulatory effect on environment-induced development of depression were found. Our data support the strong causative role of the environment modified by genetic factors, similar to animal models. Gene-environment interactions point to epigenetic factors associated with risk SNPs. Galanin-2 receptor, BDNF and X-type purin-7 receptor could be drug targets for new antidepressants.

Item Type: Article
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria
Depositing User: Dr Xenia Gonda
Date Deposited: 25 Sep 2018 14:28
Last Modified: 25 Sep 2018 14:28
URI: http://real.mtak.hu/id/eprint/85289

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