<h3>Importance</h3> 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. <h3>Objective</h3> To estimate the additive genetic, maternal, and environmental effects in ASD. <h3>Design, Setting, and Participants</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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. <h3>Conclusions and Relevance</h3> 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.

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