Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort | Autism Spectrum Disorders | JAMA Psychiatry | JAMA Network
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Original Investigation
July 17, 2019

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

Author Affiliations
  • 1Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR
  • 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 3Center for Health Communities, Environmental Health Investigations Branch, California Department of Public Health, Richmond
  • 4Department of Child Psychiatry, Turku University, Turku University Hospital, Turku, Finland
  • 5Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, Australia
  • 6Ministry of Health, Israel
  • 7Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
  • 8Seaver Autism Center for Research and Treatment at Mount Sinai, New York, New York
  • 9Information Services Department, National Institute for Health and Welfare, Helsinki, Finland
  • 10Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
  • 11Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York
  • 12Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
  • 13Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
  • 14The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York
  • 15Department of Public Health, Aarhus University, Aarhus, Denmark
  • 16Department of Economics and Business, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark
  • 17iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark
  • 18Department of Community Mental Health, University of Haifa, Haifa, Israel
  • 19Meuhedet Health Services, Israel
  • 20Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
  • 21New York State Psychiatric Institute, New York
  • 22Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark
JAMA Psychiatry. 2019;76(10):1035-1043. doi:10.1001/jamapsychiatry.2019.1411
Key Points

Question  What are the etiological origins of autism spectrum disorder?

Findings  In a large population-based multinational cohort study including more than 2 million individuals, 22 156 of whom were diagnosed with ASD, the heritability of autism spectrum disorder was estimated to be approximately 80%, with possible modest differences in the sources of autism spectrum disorder risk replicated across countries.

Meaning  The variation in the occurrence of autism spectrum disorder in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects.


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 2 001 631 individuals, of whom 1 027 546 (51.3%) were male. Among the entire sample, 22 156 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.