Epigenetics of autism-related impairment: Copy number variation and maternal infection

Varvara Mazina, Jennifer Gerdts, Sandy Trinh, Katy Ankenman, Tracey Ward, Megan Y. Dennis, Santhosh Girirajan, Evan E. Eichler, Raphael Bernier

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

OBJECTIVE: Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. METHODS: We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. RESULTS: We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. CONCLUSIONS: Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalJournal of Developmental and Behavioral Pediatrics
Volume36
Issue number2
DOIs
StatePublished - Feb 13 2015

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Autistic Disorder
Epigenomics
Mothers
Infection
Fever
Pregnancy
Interviews
Gene-Environment Interaction
Comparative Genomic Hybridization
Autism Spectrum Disorder
Genetic Predisposition to Disease
Fetal Development
History
Brain

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental and Educational Psychology
  • Psychiatry and Mental health

Cite this

Mazina, Varvara ; Gerdts, Jennifer ; Trinh, Sandy ; Ankenman, Katy ; Ward, Tracey ; Dennis, Megan Y. ; Girirajan, Santhosh ; Eichler, Evan E. ; Bernier, Raphael. / Epigenetics of autism-related impairment : Copy number variation and maternal infection. In: Journal of Developmental and Behavioral Pediatrics. 2015 ; Vol. 36, No. 2. pp. 61-67.
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Mazina, V, Gerdts, J, Trinh, S, Ankenman, K, Ward, T, Dennis, MY, Girirajan, S, Eichler, EE & Bernier, R 2015, 'Epigenetics of autism-related impairment: Copy number variation and maternal infection', Journal of Developmental and Behavioral Pediatrics, vol. 36, no. 2, pp. 61-67. https://doi.org/10.1097/DBP.0000000000000126

Epigenetics of autism-related impairment : Copy number variation and maternal infection. / Mazina, Varvara; Gerdts, Jennifer; Trinh, Sandy; Ankenman, Katy; Ward, Tracey; Dennis, Megan Y.; Girirajan, Santhosh; Eichler, Evan E.; Bernier, Raphael.

In: Journal of Developmental and Behavioral Pediatrics, Vol. 36, No. 2, 13.02.2015, p. 61-67.

Research output: Contribution to journalArticle

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AU - Ward, Tracey

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AU - Bernier, Raphael

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N2 - OBJECTIVE: Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. METHODS: We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. RESULTS: We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. CONCLUSIONS: Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.

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