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MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD.

Nieratschker V, Massart R, Gilles M, Luoni A, Suderman MJ, Krumm B, Meier S, Witt SH, Nöthen MM, Suomi SJ, Peus V, Scharnholz B, Dukal H, Hohmeyer C, Wolf IA, Cirulli F, Gass P, Sütterlin MW, Filsinger B, Laucht M, Riva MA, Rietschel M, Deuschle M, Szyf M - Transl Psychiatry (2014)

Bottom Line: Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms.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.

View Article: PubMed Central - PubMed

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.

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.

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The bar graph shows the mean methylation levels in the ELS and control group for each of the six CpG sites in MORC1, as determined by pyrosequencing. In addition, the average methylation level of all sites is displayed. Error bars represent s.e.m. No significant difference between the ELS and Ctrl group was detected. Statistical significance was calculated using the Mann–Whitney U-test. Ctrl, control group; ELS, early life stress; MORC1, MORC family CW-type zinc finger 1.
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fig2: The bar graph shows the mean methylation levels in the ELS and control group for each of the six CpG sites in MORC1, as determined by pyrosequencing. In addition, the average methylation level of all sites is displayed. Error bars represent s.e.m. No significant difference between the ELS and Ctrl group was detected. Statistical significance was calculated using the Mann–Whitney U-test. Ctrl, control group; ELS, early life stress; MORC1, MORC family CW-type zinc finger 1.

Mentions: In the human cohort, we attempted to validate the MeDIP results using a pyrosequencing approach. Pyrosequencing revealed very high methylation levels and the significant difference between the ELS and controls was not replicated (Figure 2).


MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD.

Nieratschker V, Massart R, Gilles M, Luoni A, Suderman MJ, Krumm B, Meier S, Witt SH, Nöthen MM, Suomi SJ, Peus V, Scharnholz B, Dukal H, Hohmeyer C, Wolf IA, Cirulli F, Gass P, Sütterlin MW, Filsinger B, Laucht M, Riva MA, Rietschel M, Deuschle M, Szyf M - Transl Psychiatry (2014)

The bar graph shows the mean methylation levels in the ELS and control group for each of the six CpG sites in MORC1, as determined by pyrosequencing. In addition, the average methylation level of all sites is displayed. Error bars represent s.e.m. No significant difference between the ELS and Ctrl group was detected. Statistical significance was calculated using the Mann–Whitney U-test. Ctrl, control group; ELS, early life stress; MORC1, MORC family CW-type zinc finger 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150246&req=5

fig2: The bar graph shows the mean methylation levels in the ELS and control group for each of the six CpG sites in MORC1, as determined by pyrosequencing. In addition, the average methylation level of all sites is displayed. Error bars represent s.e.m. No significant difference between the ELS and Ctrl group was detected. Statistical significance was calculated using the Mann–Whitney U-test. Ctrl, control group; ELS, early life stress; MORC1, MORC family CW-type zinc finger 1.
Mentions: In the human cohort, we attempted to validate the MeDIP results using a pyrosequencing approach. Pyrosequencing revealed very high methylation levels and the significant difference between the ELS and controls was not replicated (Figure 2).

Bottom Line: Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus