Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)

Hongyan Ren; Chiara Fabbri; Rudolf Uher; Marcella Rietschel; Ole Mors; Neven Henigsberg; Joanna Hauser; Astrid Zobel; Wolfgang Maier; Mojca Z. Dernovsek; Daniel Souery; Annamaria Cattaneo; Gerome Breen; Ian W. Craig; Anne E. Farmer; Peter McGuffin; Cathryn M. Lewis; Katherine J. Aitchison

doi:10.1038/s41398-018-0198-3

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)

Hongyan Ren, Chiara Fabbri, Rudolf Uher, Marcella Rietschel, Ole Mors, Neven Henigsberg, Joanna Hauser, Astrid Zobel, Wolfgang Maier, Mojca Z. Dernovsek, Daniel Souery, Annamaria Cattaneo, Gerome Breen, Ian W. Craig, Anne E. Farmer, Peter McGuffin, Cathryn M. Lewis, Katherine J. Aitchison

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

18 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	150
Publicación	Translational Psychiatry
Volumen	8
N.º	1
DOI	https://doi.org/10.1038/s41398-018-0198-3
Estado	Published - dic. 1 2018

Nota bibliográfica

Funding Information:
H.Y.R. was funded to conduct this analysis by the Government of Alberta (an Alberta Centennial Addiction and Mental Health Research Chair to KJA). R.U. was supported by the Canada Research Chairs Program. The GENDEP project was supported by a European Commission Framework 6 grant (contract reference: LSHB-CT-2003-503428). Lundbeck provided nortriptyline and escitalopram for the GENDEP study free of charge and with no stipulations; GlaxoSmithKline contributed to the funding of the genotyping of part of the sample; neither of these companies had any role in the data analysis reported herein nor interpretation thereof. This report therefore represents independent research part-funded by the funders named in addition to the European Commission, with funders also including the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or of any other contributing funders. The funders had no role in the design and conduct of the study, in data collection, analysis, interpretation or manuscript drafting.

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus Subject Areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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Ren, H., Fabbri, C., Uher, R., Rietschel, M., Mors, O., Henigsberg, N., Hauser, J., Zobel, A., Maier, W., Dernovsek, M. Z., Souery, D., Cattaneo, A., Breen, G., Craig, I. W., Farmer, A. E., McGuffin, P., Lewis, C. M., & Aitchison, K. J. (2018). Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP). Translational Psychiatry, 8(1), Artículo 150. https://doi.org/10.1038/s41398-018-0198-3

Ren, H, Fabbri, C, Uher, R, Rietschel, M, Mors, O, Henigsberg, N, Hauser, J, Zobel, A, Maier, W, Dernovsek, MZ, Souery, D, Cattaneo, A, Breen, G, Craig, IW, Farmer, AE, McGuffin, P, Lewis, CM & Aitchison, KJ 2018, 'Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)', Translational Psychiatry, vol. 8, n.º 1, 150. https://doi.org/10.1038/s41398-018-0198-3

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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{\textquoteright}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. ",

author = "Hongyan Ren and Chiara Fabbri and Rudolf Uher and Marcella Rietschel and Ole Mors and Neven Henigsberg and Joanna Hauser and Astrid Zobel and Wolfgang Maier and Dernovsek, {Mojca Z.} and Daniel Souery and Annamaria Cattaneo and Gerome Breen and Craig, {Ian W.} and Farmer, {Anne E.} and Peter McGuffin and Lewis, {Cathryn M.} and Aitchison, {Katherine J.}",

note = "Funding Information: H.Y.R. was funded to conduct this analysis by the Government of Alberta (an Alberta Centennial Addiction and Mental Health Research Chair to KJA). R.U. was supported by the Canada Research Chairs Program. The GENDEP project was supported by a European Commission Framework 6 grant (contract reference: LSHB-CT-2003-503428). Lundbeck provided nortriptyline and escitalopram for the GENDEP study free of charge and with no stipulations; GlaxoSmithKline contributed to the funding of the genotyping of part of the sample; neither of these companies had any role in the data analysis reported herein nor interpretation thereof. This report therefore represents independent research part-funded by the funders named in addition to the European Commission, with funders also including the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or of any other contributing funders. The funders had no role in the design and conduct of the study, in data collection, analysis, interpretation or manuscript drafting. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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AU - Ren, Hongyan

AU - Fabbri, Chiara

AU - Uher, Rudolf

AU - Rietschel, Marcella

AU - Mors, Ole

AU - Henigsberg, Neven

AU - Hauser, Joanna

AU - Zobel, Astrid

AU - Maier, Wolfgang

AU - Dernovsek, Mojca Z.

AU - Souery, Daniel

AU - Cattaneo, Annamaria

AU - Breen, Gerome

AU - Craig, Ian W.

AU - Farmer, Anne E.

AU - McGuffin, Peter

AU - Lewis, Cathryn M.

AU - Aitchison, Katherine J.

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Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP)

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ASJC Scopus Subject Areas

ODS de las Naciones Unidas

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