Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.
Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored. The current study aimed to evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their psychopathological status. Data from the Illumina Infinium HumanMethylation450 Beadchip was used to evaluate peripheral blood DNA methylation of 34 twins (17 MZ pairs). Two analytical strategies were used to identify (a) differentially methylated probes (DMPs) and (b) variably methylated probes (VMPs). Most DMPs were located in genes previously related to neuropsychiatric phenotypes. Remarkably, one of these DMPs (cg01122889) was located in the WDR26 gene, the DNA sequence of which has been implicated in major depressive disorder from genome-wide association studies. Expression of WDR26 has also been proposed as a biomarker of depression in human blood. Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling. These results expand on previous research to indicate that both differential methylation and differential variability have a role in the etiology and clinical manifestation of depression, and provide clues on specific genomic loci of potential interest in the epigenetics of depression.
1] Unitat [dacute ]Antropologia, Departament de Biologia Animal, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain [2] Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
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Córdova-Palomera
1] Unitat [dacute ]Antropologia, Departament de Biologia Animal, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain [2] Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
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Fatjó-Vilas
1] Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain [2] Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain [3] Departamento de Psiquiatría and Instituto Clínico de Neurociencias (ICN), Hospital Clínico, Barcelona, Spain.
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Gastó
1] Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain [2] Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain [3] Departamento de Psiquiatría and Instituto Clínico de Neurociencias (ICN), Hospital Clínico, Barcelona, Spain.
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Navarro
1] Université Paris Descartes, PRES Paris Sorbonne Cité, INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France [2] Hôpital Sainte-Anne, Service Hospitalo-Universitaire, Faculté de Médecine Paris Descartes, Paris, France [3] GDR3557-Institut de Psychiatrie, Paris, France.
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Krebs
1] Unitat [dacute ]Antropologia, Departament de Biologia Animal, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain [2] Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
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Fañanás
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020746:Calcium Channels, L-Type / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D008875:Middle Aged; D048290:Mitogen-Activated Protein Kinase 11 / Q000235:genetics; D011506:Proteins / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics* / Q000523:psychology; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; C035170:IGF2 protein, human; D011506:Proteins; C543172:WDR26 protein, human; D007335:Insulin-Like Growth Factor II; D048290:Mitogen-Activated Protein Kinase 11