Integrative DNA Methylation and Gene Expression Analysis in the Prefrontal Cortex of Mexicans Who Died by Suicide
Por:
Romero-Pimentel A.L., Almeida D., Munõz-Montero S., Rangel C., Mendoza-Morales R., Gonzalez-Saenz E.E., Nagy C., Chen G., Aouabed Z., Theroux J.-F., Turecki G., Martinez-Levy G., Walss-Bass C., Monroy-Jaramillo N., Fernández-Figueroa E.A., Gómez-Cotero A., Garciá-Dolores F., Morales-Marin M.E., Nicolini H.
Publicada:
1 ene 2021
Resumen:
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. © 2021 The Author(s). Published by Oxford University Press on behalf of CINP.
Filiaciones:
Romero-Pimentel A.L.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
McGill Group of Suicide Studies, Montreal, Canada
Almeida D.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Munõz-Montero S.:
Facultad de Psicología, Universidad Nacional Autónoma de México, México City, Mexico
Rangel C.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Mendoza-Morales R.:
Instituto de Ciencias Forenses del Tribunal Superior de Justicia de la CDMX, Mexico City, Mexico
Gonzalez-Saenz E.E.:
Instituto de Ciencias Forenses del Tribunal Superior de Justicia de la CDMX, Mexico City, Mexico
Nagy C.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Chen G.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Aouabed Z.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Theroux J.-F.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Turecki G.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Martinez-Levy G.:
Psychiatric Genetics Department, Clinical Research Branch, National Institute of Psychiatry Ramón de la Fuente, Mexico City, Mexico
Walss-Bass C.:
Louis A. Faillace, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
Monroy-Jaramillo N.:
Department of Neurogenetics, National Institute of Neurology and Neurosurgery, Manuel Velasco Suarez, Mexico City, Mexico
Fernández-Figueroa E.A.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Gómez-Cotero A.:
Centro Interdisciplinario de Ciencias de la Salud, Instituto Politécnico Nacional, Unidad Santo Tomás, Mexico City, Mexico
Garciá-Dolores F.:
Instituto de Ciencias Forenses del Tribunal Superior de Justicia de la CDMX, Mexico City, Mexico
Morales-Marin M.E.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
Nicolini H.:
Laboratorio de Genómica de Enfermedades Psiquiátricas y neurodegenerativas, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan Ciudad de México, CDMX, Tlalpan, 14610, Mexico
All Open Access, Gold
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