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Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients

Depression is common among late-onset Alzheimer’s Disease (LOAD) patients. Only a few studies investigated the genetic variability underlying the comorbidity of depression in LOAD. Moreover, the epigenetic and transcriptomic factors that may contribute to comorbid depression in LOAD have yet to be s...

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Autores principales: Upadhya, Suraj, Gingerich, Daniel, Lutz, Michael William, Chiba-Falek, Ornit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687527/
https://www.ncbi.nlm.nih.gov/pubmed/36421693
http://dx.doi.org/10.3390/biom12111679
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author Upadhya, Suraj
Gingerich, Daniel
Lutz, Michael William
Chiba-Falek, Ornit
author_facet Upadhya, Suraj
Gingerich, Daniel
Lutz, Michael William
Chiba-Falek, Ornit
author_sort Upadhya, Suraj
collection PubMed
description Depression is common among late-onset Alzheimer’s Disease (LOAD) patients. Only a few studies investigated the genetic variability underlying the comorbidity of depression in LOAD. Moreover, the epigenetic and transcriptomic factors that may contribute to comorbid depression in LOAD have yet to be studied. Using transcriptomic and DNA-methylomic datasets from the ROSMAP cohorts, we investigated differential gene expression and DNA-methylation in LOAD patients with and without comorbid depression. Differential expression analysis did not reveal significant association between differences in gene expression and the risk of depression in LOAD. Upon sex-stratification, we identified 25 differential expressed genes (DEG) in males, of which CHI3L2 showed the strongest upregulation, and only 3 DEGs in females. Additionally, testing differences in DNA-methylation found significant hypomethylation of CpG (cg20442550) on chromosome 17 (log(2)FC = −0.500, p = 0.004). Sex-stratified differential DNA-methylation analysis did not identify any significant CpG probes. Integrating the transcriptomic and DNA-methylomic datasets did not discover relationships underlying the comorbidity of depression and LOAD. Overall, our study is the first multi-omics genome-wide exploration of the role of gene expression and epigenome alterations in the risk of comorbid depression in LOAD patients. Furthermore, we discovered sex-specific differences in gene expression underlying the risk of depression symptoms in LOAD.
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spelling pubmed-96875272022-11-25 Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients Upadhya, Suraj Gingerich, Daniel Lutz, Michael William Chiba-Falek, Ornit Biomolecules Article Depression is common among late-onset Alzheimer’s Disease (LOAD) patients. Only a few studies investigated the genetic variability underlying the comorbidity of depression in LOAD. Moreover, the epigenetic and transcriptomic factors that may contribute to comorbid depression in LOAD have yet to be studied. Using transcriptomic and DNA-methylomic datasets from the ROSMAP cohorts, we investigated differential gene expression and DNA-methylation in LOAD patients with and without comorbid depression. Differential expression analysis did not reveal significant association between differences in gene expression and the risk of depression in LOAD. Upon sex-stratification, we identified 25 differential expressed genes (DEG) in males, of which CHI3L2 showed the strongest upregulation, and only 3 DEGs in females. Additionally, testing differences in DNA-methylation found significant hypomethylation of CpG (cg20442550) on chromosome 17 (log(2)FC = −0.500, p = 0.004). Sex-stratified differential DNA-methylation analysis did not identify any significant CpG probes. Integrating the transcriptomic and DNA-methylomic datasets did not discover relationships underlying the comorbidity of depression and LOAD. Overall, our study is the first multi-omics genome-wide exploration of the role of gene expression and epigenome alterations in the risk of comorbid depression in LOAD patients. Furthermore, we discovered sex-specific differences in gene expression underlying the risk of depression symptoms in LOAD. MDPI 2022-11-12 /pmc/articles/PMC9687527/ /pubmed/36421693 http://dx.doi.org/10.3390/biom12111679 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Upadhya, Suraj
Gingerich, Daniel
Lutz, Michael William
Chiba-Falek, Ornit
Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title_full Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title_fullStr Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title_full_unstemmed Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title_short Differential Gene Expression and DNA Methylation in the Risk of Depression in LOAD Patients
title_sort differential gene expression and dna methylation in the risk of depression in load patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687527/
https://www.ncbi.nlm.nih.gov/pubmed/36421693
http://dx.doi.org/10.3390/biom12111679
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