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. 2019 Oct 1;76(10):1035-1043.
doi: 10.1001/jamapsychiatry.2019.1411.

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

Dan Bai  1 , Benjamin Hon Kei Yip  1   2 , Gayle C Windham  3 , Andre Sourander  4 , Richard Francis  5 , Rinat Yoffe  6 , Emma Glasson  5 , Behrang Mahjani  2   7   8 , Auli Suominen  4 , Helen Leonard  5 , Mika Gissler  4   9   10 , Joseph D Buxbaum  7   8   11   12   13   14 , Kingsley Wong  5 , Diana Schendel  15   16   17 , Arad Kodesh  18   19 , Michaeline Breshnahan  20   21 , Stephen Z Levine  18 , Erik T Parner  22 , Stefan N Hansen  22 , Christina Hultman  2 , Abraham Reichenberg  7   8   11   14 , Sven Sandin  2   7   8
Affiliations

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

Dan Bai et al. JAMA Psychiatry. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Windham reported receiving grants from NIH sub-contract during the conduct of the study. Dr Sourander reported receiving grants from Academy of Finland Flagship Programme (decision No. 320162), Academy of Finland (decision No. 308552), the National Institutes of Health (NIH; W81XWH-17-1-0566 ), and the NIH (1U01HD073978-01) during the conduct of the study. Dr Francis reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and the National Institute of Neurological Disorders and Stroke during the conduct of the study. Ms Yoffe reported employment with the Israeli Ministry of Health, which did not fund the current research. Dr Leonard reported being a National Health and Medical Research Council Senior Research Fellow. Dr Buxbaum reported receiving grants from the Seaver Foundation during the conduct of the study. Dr Wong reported receiving grants from the NIH during the conduct of the study and grants from NHMRC outside the submitted work. Dr Breshnahan reported receiving grants from Columbia University during the conduct of the study. Dr Levine reported receiving research support from Shire Pharmaceuticals unrelated to the current research more than 3 years ago. Dr Sandin reported receiving grants from NIH during the conduct of the study. Dr Sandin reported being a Faculty Fellow of the Beatrice and Samuel A. Seaver Foundation. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Variance Component Derivation From Correlations Between Family Members
Circles represent female and squares represent male family members. Curved arrows indicate family relationships used in the calculations. A indicates additive genetic effect; C, shared environmental effect; E, nonshared environmental effect; M, maternal effect; and mPCs, maternal parallel cousins. aHalf siblings were excluded from the main analysis based on the assumption on shared environmental effect, which assumes children always live with their mother, and all 4 variance components can be estimated with full siblings and cousins (mPCs and cousins of other relationships). bTwins were excluded from the present study owing to lack of information about zygosity status.
Figure 2.
Figure 2.. Autism Spectrum Disorder (ASD): Estimated Shared Environmental and Maternal Effect (2-Sided 95% CI) for Denmark, Finland, Sweden, and Nordic Countries Combined
All estimates are recalculated to fraction of variation explained. A indicates additive genetic effect; C, shared environmental effect; E, nonshared environmental effect; and M, maternal effect.
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Comment in

References

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