Integrative DNA Methylation and Gene Expression Analysis in the Prefrontal Cortex of Mexicans Who Died by Suicide
| Autor: | Gabriela Martinez-Levy, Eli Elier González-Sáenz, Gustavo Turecki, Amalia Gómez-Cotero, Zahia Aouabed, Said Muñoz-Montero, Gary Chen, Daniel Almeida, Claudia Rangel, Consuelo Walss-Bass, Ana Luisa Romero-Pimentel, Nancy Monroy-Jaramillo, Corina Nagy, Humberto Nicolini, Mirna Edith Morales-Marín, Fernando García-Dolores, Roberto Cuauhtemoc Mendoza-Morales, Edith A. Fernández-Figueroa, Jean-François Théroux |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male AcademicSubjects/MED00415 Bisulfite sequencing Gene Expression Prefrontal Cortex Biology Sudden death Regular Research Articles Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Gene expression Humans Pharmacology (medical) Prefrontal cortex Gene Mexico postmortem human brain Pharmacology Genetics Molecular pathology AcademicSubjects/SCI01870 Methylation DNA Methylation Psychiatry and Mental health Suicide 030104 developmental biology Case-Control Studies DNA methylation Epigenomics/transcriptomics 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 1461-1457 |
| Popis: | Background Suicide represents a major health concern, especially in developing countries. While many demographic risk factors have been proposed, the underlying molecular pathology of suicide remains poorly understood. A body of evidence suggests that aberrant DNA methylation and expression is involved. In this study, we examined DNA methylation profiles and concordant gene expression changes in the prefrontal cortex of Mexicans who died by suicide. Methods In collaboration with the coroner’s office in Mexico City, brain samples of males who died by suicide (n = 35) and age-matched sudden death controls (n = 13) were collected. DNA and RNA were extracted from prefrontal cortex tissue and analyzed with the Infinium Methylation480k and the HumanHT-12 v4 Expression Beadchips, respectively. Results We report evidence of altered DNA methylation profiles at 4430 genomic regions together with 622 genes characterized by differential expression in cases vs controls. Seventy genes were found to have concordant methylation and expression changes. Metacore-enriched analysis identified 10 genes with biological relevance to psychiatric phenotypes and suicide (ADCY9, CRH, NFATC4, ABCC8, HMGA1, KAT2A, EPHA2, TRRAP, CD22, and CBLN1) and highlighted the association that ADCY9 has with various pathways, including signal transduction regulated by the cAMP-responsive element modulator, neurophysiological process regulated by the corticotrophin-releasing hormone, and synaptic plasticity. We therefore went on to validate the observed hypomethylation of ADCY9 in cases vs control through targeted bisulfite sequencing. Conclusion Our study represents the first, to our knowledge, analysis of DNA methylation and gene expression associated with suicide in a Mexican population using postmortem brain, providing novel insights for convergent molecular alterations associated with suicide. |
| Databáze: | OpenAIRE |
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