Ren, Hongyan and Fabbri, Chiara and Uher, Rudolf and Rietschel, Marcella and Mors, Ole and Henigsberg, Neven and Hauser, Joanna and Zobel, Astrid and Maier, Wolfgang and Dernovsek, Mojca Z. and Souery, Daniel and Cattaneo, Annamaria and Breen, Gerome and Craig, Ian W. and Farmer, Anne E. and McGuffin, Peter and Lewis, Cathryn M. and Aitchison, Katherine J. (2018) Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP). Translational Psychiatry, 8 (1). p. 150. ISSN 2158-3188
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Abstract
A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2.07 × 10-9) while gene-set enrichment analysis returned one gene ontology term, axon cargo transport (GO: 0008088) with a nominally significant P value (1.15 × 10-5). Furthermore, our exploratory analysis yielded some interesting, albeit not statistically significant genetic correlation with Parkinson's Disease and nucleus accumbens gray matter. In addition, polygenic risk scores (PRSs) generated from our association analysis were found to be able to predict treatment efficacy of the antidepressants in this study. In conclusion, we found some markers significantly associated with anhedonia, and some suggestive findings of related pathways and biological functions, which could be further investigated in other studies.
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| Additional Information: | © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any mediumor format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changesweremade. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | ||||||||||||||||||||||||||||||||||||||
| MeSH: | Adult ; Anhedonia ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/psychology ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gray Matter/pathology ; Humans ; Male ; Middle Aged ; Multifactorial Inheritance ; Nucleus Accumbens/pathology ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases/genetics ; Regression Analysis ; Ribonucleoprotein, U4-U6 Small Nuclear/genetics ; Risk Assessment | ||||||||||||||||||||||||||||||||||||||
| Departments: | Hrvatski institut za istraživanje mozga Katedra za psihijatriju i psihološku medicinu |
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| Depositing User: | Anja Majstorović | ||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||
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| Date: | 13 August 2018 | ||||||||||||||||||||||||||||||||||||||
| Date Deposited: | 21 Jun 2019 09:50 | ||||||||||||||||||||||||||||||||||||||
| Last Modified: | 21 Jun 2019 09:50 | ||||||||||||||||||||||||||||||||||||||
| Subjects: | / | ||||||||||||||||||||||||||||||||||||||
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| URI: | http://medlib.mef.hr/id/eprint/3291 |
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