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. 2018 Apr 1;83(7):589-597.
doi: 10.1016/j.biopsych.2017.09.007. Epub 2017 Sep 21.

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

Benjamin Hon Kei Yip  1 , Dan Bai  2 , Behrang Mahjani  3 , Lambertus Klei  4 , Yudi Pawitan  3 , Christina M Hultman  3 , Dorothy E Grice  5 , Kathryn Roeder  6 , Joseph D Buxbaum  7 , Bernie Devlin  4 , Abraham Reichenberg  8 , Sven Sandin  9
Affiliations

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

Benjamin Hon Kei Yip et al. Biol Psychiatry. .

Abstract

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.

Keywords: Autism; Epidemiology; Genetics; Heritability; Population-based; Psychiatry.

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Conflict of interest statement

DISCLOSURES

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart describing the study population. AD, autistic disorder; ASD, autism spectrum disorder; ID, identification; SD, Asperger and pervasive development disorders not otherwise specified combined.
Figure 2
Figure 2
Family recurrence risk ratio (FRR) with 95% confidence intervals (CIs), by outcome and type of sibling/cousin relations. AD, autistic disorder; ASD, autism spectrum disorder; SD, Asperger and pervasive development disorders not otherwise specified combined.
Figure 3
Figure 3
Fraction of total variation explained by each variance component with 95% confidence interval (CI), by outcome. AD, autistic disorder; ASD, autism spectrum disorder; SD, Asperger and pervasive development disorders not otherwise specified combined.
See this image and copyright information in PMC

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