| Abstract |
schizophreniais one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220schizophrenia病人;220 age-matched healthy controls; 110 femaleschizophrenia病人;110 age-matched healthy females; 110 maleschizophrenia病人;110的同龄的健康男性。我们也investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile betweenschizophreniaand control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2,FNDC4and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles betweenschizophreniapatients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role inschizophreniapathogenesis. |