TY - JOUR
T1 - Heritable Variation, With Little or No Maternal Effect, Accounts for Recurrence Risk to Autism Spectrum Disorder in Sweden
AU - Yip, Benjamin Hon Kei
AU - Bai, Dan
AU - Mahjani, Behrang
AU - Klei, Lambertus
AU - Pawitan, Yudi
AU - Hultman, Christina M.
AU - Grice, Dorothy E.
AU - Roeder, Kathryn
AU - Buxbaum, Joseph D.
AU - Devlin, Bernie
AU - Reichenberg, Abraham
AU - Sandin, Sven
N1 - Publisher Copyright:
© 2017 Society of Biological Psychiatry
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - Autism
KW - Epidemiology
KW - Genetics
KW - Heritability
KW - Population-based
KW - Psychiatry
UR - http://www.scopus.com/inward/record.url?scp=85032932944&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2017.09.007
DO - 10.1016/j.biopsych.2017.09.007
M3 - Article
C2 - 29100626
AN - SCOPUS:85032932944
SN - 0006-3223
VL - 83
SP - 589
EP - 597
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 7
ER -