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Association between DNA methylation levels in brain tissue and late-life depression in community-based participants

OBJECTIVE: Major depressive disorder (MDD) arises from a combination of genetic and environmental risk factors and DNA methylation is one of the molecular mechanisms through which these factors can manifest. However, little is known about the epigenetic signature of MDD in brain tissue. This study a...

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Autores principales: Hüls, Anke, Robins, Chloe, Conneely, Karen N., De Jager, Philip L., Bennett, David A., Epstein, Michael P., Wingo, Thomas S., Wingo, Aliza P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393126/
https://www.ncbi.nlm.nih.gov/pubmed/32733030
http://dx.doi.org/10.1038/s41398-020-00948-6
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author Hüls, Anke
Robins, Chloe
Conneely, Karen N.
De Jager, Philip L.
Bennett, David A.
Epstein, Michael P.
Wingo, Thomas S.
Wingo, Aliza P.
author_facet Hüls, Anke
Robins, Chloe
Conneely, Karen N.
De Jager, Philip L.
Bennett, David A.
Epstein, Michael P.
Wingo, Thomas S.
Wingo, Aliza P.
author_sort Hüls, Anke
collection PubMed
description OBJECTIVE: Major depressive disorder (MDD) arises from a combination of genetic and environmental risk factors and DNA methylation is one of the molecular mechanisms through which these factors can manifest. However, little is known about the epigenetic signature of MDD in brain tissue. This study aimed to investigate associations between brain tissue-based DNA methylation and late-life MDD. METHODS: We performed a brain epigenome-wide association study (EWAS) of late-life MDD in 608 participants from the Religious Order Study and the Rush Memory and Aging Project (ROS/MAP) using DNA methylation profiles of the dorsal lateral prefrontal cortex generated using the Illumina HumanMethylation450 Beadchip array. We also conducted an EWAS of MDD in each sex separately. RESULTS: We found epigenome-wide significant associations between brain tissue-based DNA methylation and late-life MDD. The most significant and robust association was found with altered methylation levels in the YOD1 locus (cg25594636, p value = 2.55 × 10(−11); cg03899372, p value = 3.12 × 10(−09); cg12796440, p value = 1.51 × 10(−08), cg23982678, p value = 7.94 × 10(−08)). Analysis of differentially methylated regions (p value = 5.06 × 10(−10)) further confirmed this locus. Other significant loci include UGT8 (cg18921206, p value = 1.75 × 10(−08)), FNDC3B (cg20367479, p value = 4.97 × 10(−08)) and SLIT2 (cg10946669, p value = 8.01 × 10(−08)). Notably, brain tissue-based methylation levels were strongly associated with late-life MDD in men more than in women. CONCLUSIONS: We identified altered methylation in the YOD1, UGT8, FNDC3B, and SLIT2 loci as new epigenetic factors associated with late-life MDD. Furthermore, our study highlights the sex-specific molecular heterogeneity of MDD.
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spelling pubmed-73931262020-08-12 Association between DNA methylation levels in brain tissue and late-life depression in community-based participants Hüls, Anke Robins, Chloe Conneely, Karen N. De Jager, Philip L. Bennett, David A. Epstein, Michael P. Wingo, Thomas S. Wingo, Aliza P. Transl Psychiatry Article OBJECTIVE: Major depressive disorder (MDD) arises from a combination of genetic and environmental risk factors and DNA methylation is one of the molecular mechanisms through which these factors can manifest. However, little is known about the epigenetic signature of MDD in brain tissue. This study aimed to investigate associations between brain tissue-based DNA methylation and late-life MDD. METHODS: We performed a brain epigenome-wide association study (EWAS) of late-life MDD in 608 participants from the Religious Order Study and the Rush Memory and Aging Project (ROS/MAP) using DNA methylation profiles of the dorsal lateral prefrontal cortex generated using the Illumina HumanMethylation450 Beadchip array. We also conducted an EWAS of MDD in each sex separately. RESULTS: We found epigenome-wide significant associations between brain tissue-based DNA methylation and late-life MDD. The most significant and robust association was found with altered methylation levels in the YOD1 locus (cg25594636, p value = 2.55 × 10(−11); cg03899372, p value = 3.12 × 10(−09); cg12796440, p value = 1.51 × 10(−08), cg23982678, p value = 7.94 × 10(−08)). Analysis of differentially methylated regions (p value = 5.06 × 10(−10)) further confirmed this locus. Other significant loci include UGT8 (cg18921206, p value = 1.75 × 10(−08)), FNDC3B (cg20367479, p value = 4.97 × 10(−08)) and SLIT2 (cg10946669, p value = 8.01 × 10(−08)). Notably, brain tissue-based methylation levels were strongly associated with late-life MDD in men more than in women. CONCLUSIONS: We identified altered methylation in the YOD1, UGT8, FNDC3B, and SLIT2 loci as new epigenetic factors associated with late-life MDD. Furthermore, our study highlights the sex-specific molecular heterogeneity of MDD. Nature Publishing Group UK 2020-07-30 /pmc/articles/PMC7393126/ /pubmed/32733030 http://dx.doi.org/10.1038/s41398-020-00948-6 Text en © The Author(s) 2020 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 medium or 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 changes were made. 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/.
spellingShingle Article
Hüls, Anke
Robins, Chloe
Conneely, Karen N.
De Jager, Philip L.
Bennett, David A.
Epstein, Michael P.
Wingo, Thomas S.
Wingo, Aliza P.
Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title_full Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title_fullStr Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title_full_unstemmed Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title_short Association between DNA methylation levels in brain tissue and late-life depression in community-based participants
title_sort association between dna methylation levels in brain tissue and late-life depression in community-based participants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393126/
https://www.ncbi.nlm.nih.gov/pubmed/32733030
http://dx.doi.org/10.1038/s41398-020-00948-6
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