title: Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases.
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.
authors.affiliation: Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Maschietto
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Laura Caroline
authors.initials: LC
authors.lastname: Bastos
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Tahira
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Elen Pereira
authors.initials: EP
authors.lastname: Bastos
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Veronica Luiza Vale
authors.initials: VL
authors.lastname: Euclydes
authors.affiliation: Department of Pediatrics, University of São Paulo Medical School, SP, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Brentani
authors.affiliation: Department of Global Health and Population, Harvard School of Public Health, USA.
authors.forename: Günther
authors.initials: G
authors.lastname: Fink
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Angelica
authors.initials: A
authors.lastname: de Baumont
authors.affiliation: Department of Pathology, University Hospital of Sao Paulo, SP, Brazil.
authors.forename: Aloísio
authors.initials: A
authors.lastname: Felipe-Silva
authors.affiliation: Department of Obstetrics and Gynecology, University of São Paulo Medical School, SP, Brazil.
authors.forename: Rossana Pulcineli Vieira
authors.initials: RP
authors.lastname: Francisco
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Gouveia
authors.affiliation: Department of Pediatrics, University of São Paulo Medical School, SP, Brazil.
authors.forename: Sandra Josefina Ferraz Ellero
authors.initials: SJ
authors.lastname: Grisi
authors.affiliation: Department of Pediatrics, University of São Paulo Medical School, SP, Brazil.
authors.forename: Ana Maria Ulhoa
authors.initials: AM
authors.lastname: Escobar
authors.affiliation: Department of Pediatrics, University of São Paulo Medical School, SP, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Moreira-Filho
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Guilherme Vanoni
authors.initials: GV
authors.lastname: Polanczyk
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Euripedes Constantino
authors.initials: EC
authors.lastname: Miguel
authors.affiliation: Institute of Psychiatry, University of São Paulo Medical School, SP, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
mesh_terms: D000328:Adult; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D001523:Mental Disorders / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D012559:Schizophrenia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D012727:Sex Characteristics; D063507:Sexism / Q000523:psychology