title: MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD.
abstract: Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD.
authors.affiliation: 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany [2] Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Nieratschker
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Massart
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gilles
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Luoni
authors.affiliation: 1] Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada [2] Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, Montreal, QC, Canada [3] McGill Centre for Bioinformatics, McGill University, Montreal, QC, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Suderman
authors.affiliation: Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Krumm
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Meier
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: S H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: 1] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany [2] Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Suomi
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Peus
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Scharnholz
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Dukal
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hohmeyer
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: I A-C
authors.initials: IA
authors.lastname: Wolf
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cirulli
authors.affiliation: Department of Psychiatry and Psychotherapy, Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Gass
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Sütterlin
authors.affiliation: Department of Obstetrics, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen am Rhein, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Filsinger
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Laucht
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Riva
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Deuschle
authors.affiliation: 1] Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada [2] Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008253:Macaca mulatta; D017397:Prefrontal Cortex / Q000378:metabolism; D011247:Pregnancy; D013045:Species Specificity; D013234:Stem Cells; D013315:Stress, Psychological / Q000150:complications*; D013601:T-Lymphocytes / Q000378:metabolism