Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases

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Maschietto, Mariana ; Bastos, Laura Caroline ; Tahira, Ana Carolina ; Bastos, Elen Pereira ; Vale Euclydes, Veronica Luiza ; Brentani, Alexandra ; Fink, Gunther ; de Baumont, Angelica ; Felipe-Silva, Alosio ; Vieira Francisco, Rossana Pulcineli ; Gouveia, Gisele ; Ferraz Ellero Grisi, Sandra Josefina ; Ulhoa Escobar, Ana Maria ; Moreira-Filho, Carlos Alberto ; Polanczyk, Guilherme Vanoni ; Miguel, Euripedes Constantino ; Brentani, Helena

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, MAR 17 2017.
• Web of Science Citations: 4

Abstract

Sex differences in the prevalence of psychiatric disorders are well documented, with exposure to stress during gestation differentially impacting females and males. We explored sex-specific DNA methylation in the cord blood of 39 females and 32 males born at term and with appropriate weight at birth regarding their potential connection to psychiatric outcomes. Mothers were interviewed to gather information about environmental factors (gestational exposure) that could interfere with the methylation profiles in the newborns. Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChips. Excluding XYS probes, there were 2,332 differentially methylated CpG sites (DMSs) between sexes, which were enriched within brain modules of co-methylated CpGs during brain development and also differentially methylated in the brains of boys and girls. Genes associated with the DMSs were enriched for neurodevelopmental disorders, particularly for CpG sites found differentially methylated in brain tissue between patients with schizophrenia and controls. Moreover, the DMS had an overlap of 890 (38%) CpG sites with a cohort submitted to toxic exposition during gestation. This study supports the evidences that sex differences in DNA methylation of autosomes act as a primary driver of sex differences that are found in psychiatric outcomes. (AU)

• FAPESP's process: 12/19472-7 - Validation of the developmental screening test proposed by the Ministry of Health - 2002
• Grantee: Sandra Josefina Ferraz Ellero Grisi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/57896-8 - National Institute for Developmental Psychiatry
• Grantee: Eurípedes Constantino Miguel Filho
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/06281-7 - CHARACTERIZATION OF THE EPIGENETIC REGULATION IN HUMAN SOLID PAEDIATRIC TUMOURS
• Grantee: Mariana Camargo Maschietto
• Support Opportunities: Scholarships in Brazil - Young Researchers