title: Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.
abstract: Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Autism Res 2017, 10: 430-438. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Jolien
authors: J
authors: Rijlaarsdam
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.|School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors: Marinus H
authors: MH
authors: van IJzendoorn
authors: Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Frank C
authors: FC
authors: Verhulst
authors: Generation R Study Group, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Vincent W V
authors: VW
authors: Jaddoe
authors: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Janine F
authors: JF
authors: Felix
authors: Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Psychiatry, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Henning
authors: H
authors: Tiemeier
authors: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands.
authors: Marian J
authors: MJ
authors: Bakermans-Kranenburg
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D011795:Surveys and Questionnaires
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
keywords: DNA methylation; autistic traits; oxytocin receptor gene (OXTR); stress exposure