Heritable Variation, With Little or No Maternal Effect, Accounts for Recurrence Risk to Autism Spectrum Disorder in Sweden

Benjamin Hon Kei Yip, Dan Bai, Behrang Mahjani, Lambertus Klei, Yudi Pawitan, Christina M. Hultman, Dorothy E. Grice, Kathryn Roeder, Joseph D. Buxbaum, Bernie Devlin, Abraham Reichenberg, Sven Sandin

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Autism spectrum disorder (ASD) has both genetic and environmental origins, including potentially maternal effects. Maternal effects describe the association of one or more maternal phenotypes with liability to ASD in progeny that are independent of maternally transmitted risk alleles. While maternal effects could play an important role, consistent with association to maternal traits such as immune status, no study has estimated maternal, additive genetic, and environmental effects in ASD. Methods: Using a population-based sample consisting of all children born in Sweden from 1998 to 2007 and their relatives, we fitted statistical models to family data to estimate the variance in ASD liability originating from maternal, additive genetic, and shared environmental effects. We calculated sibling and cousin family recurrence risk ratio as a direct measure of familial, genetic, and environmental risk factors and repeated the calculations on diagnostic subgroups, specifically autistic disorder (AD) and spectrum disorder (SD), which included Asperger's syndrome and/or pervasive developmental disorder not otherwise specified. Results: The sample consisted of 776,212 children of whom 11,231 had a diagnosis of ASD: 4554 with AD, 6677 with SD. We found support for large additive genetic contribution to liability; heritability (95% confidence interval [CI]) was estimated to 84.8% (95% CI: 73.1–87.3) for ASD, 79.6% (95% CI: 61.2–85.1) for AD, and 76.4% (95% CI: 63.0–82.5) for SD. Conclusions: There was modest, if any, contribution of maternal effects to liability for ASD, including subtypes AD and SD, and there was no support for shared environmental effects. These results show liability to ASD arises largely from additive genetic variation.

Original languageEnglish
Pages (from-to)589-597
Number of pages9
JournalBiological Psychiatry
Issue number7
StatePublished - 1 Apr 2018


  • Autism
  • Epidemiology
  • Genetics
  • Heritability
  • Population-based
  • Psychiatry


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