Association of Genetic and Environmental Factors with Autism in a 5-Country Cohort

Dan Bai, Benjamin Hon Kei Yip, Gayle C. Windham, Andre Sourander, Richard Francis, Rinat Yoffe, Emma Glasson, Behrang Mahjani, Auli Suominen, Helen Leonard, Mika Gissler, Joseph D. Buxbaum, Kingsley Wong, Diana Schendel, Arad Kodesh, Michaeline Breshnahan, Stephen Z. Levine, Erik T. Parner, Stefan N. Hansen, Christina HultmanAbraham Reichenberg, Sven Sandin

Research output: Contribution to journalArticlepeer-review


Importance: The origins and development of autism spectrum disorder (ASD) remain unresolved. No individual-level study has provided estimates of additive genetic, maternal, and environmental effects in ASD across several countries. Objective: To estimate the additive genetic, maternal, and environmental effects in ASD. Design, Setting, and Participants: Population-based, multinational cohort study including full birth cohorts of children from Denmark, Finland, Sweden, Israel, and Western Australia born between January 1, 1998, and December 31, 2011, and followed up to age 16 years. Data were analyzed from September 23, 2016 through February 4, 2018. Main Outcomes and Measures: Across 5 countries, models were fitted to estimate variance components describing the total variance in risk for ASD occurrence owing to additive genetics, maternal, and shared and nonshared environmental effects. Results: The analytic sample included 2001631 individuals, of whom 1027546 (51.3%) were male. Among the entire sample, 22156 were diagnosed with ASD. The median (95% CI) ASD heritability was 80.8% (73.2%-85.5%) for country-specific point estimates, ranging from 50.9% (25.1%-75.6%) (Finland) to 86.8% (69.8%-100.0%) (Israel). For the Nordic countries combined, heritability estimates ranged from 81.2% (73.9%-85.3%) to 82.7% (79.1%-86.0%). Maternal effect was estimated to range from 0.4% to 1.6%. Estimates of genetic, maternal, and environmental effects for autistic disorder were similar with ASD. Conclusions and Relevance: Based on population data from 5 countries, the heritability of ASD was estimated to be approximately 80%, indicating that the variation in ASD occurrence in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects. The results suggest possible modest differences in the sources of ASD risk between countries..

Original languageEnglish
Pages (from-to)1035-1043
Number of pages9
JournalJAMA Psychiatry
Issue number10
StatePublished - Oct 2019

Bibliographical note

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© 2019 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Psychiatry and Mental health


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