Dan Bai1, Benjamin Hon Kei Yip1,2, Gayle C Windham3, Andre Sourander4, Richard Francis5, Rinat Yoffe6, Emma Glasson5, Behrang Mahjani2,7,8, Auli Suominen4, Helen Leonard5, Mika Gissler4,9,10, Joseph D Buxbaum7,8,11,12,13,14, Kingsley Wong5, Diana Schendel15,16,17, Arad Kodesh18,19, Michaeline Breshnahan20,21, Stephen Z Levine18, Erik T Parner22, Stefan N Hansen22, Christina Hultman2, Abraham Reichenberg7,8,11,14, Sven Sandin2,7,8. 1. Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3. Center for Health Communities, Environmental Health Investigations Branch, California Department of Public Health, Richmond. 4. Department of Child Psychiatry, Turku University, Turku University Hospital, Turku, Finland. 5. Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, Perth, Australia. 6. Ministry of Health, Israel. 7. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York. 8. Seaver Autism Center for Research and Treatment at Mount Sinai, New York, New York. 9. Information Services Department, National Institute for Health and Welfare, Helsinki, Finland. 10. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. 11. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 12. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. 13. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York. 14. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 15. Department of Public Health, Aarhus University, Aarhus, Denmark. 16. Department of Economics and Business, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark. 17. iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark. 18. Department of Community Mental Health, University of Haifa, Haifa, Israel. 19. Meuhedet Health Services, Israel. 20. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. 21. New York State Psychiatric Institute, New York. 22. Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
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.
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.
Authors: Jens Langhoff-Roos; Lone Krebs; Kari Klungsøyr; Ragnheidur I Bjarnadottir; Karin Källén; Anna-Maija Tapper; Maija Jakobsson; Per E Børdahl; Pelle G Lindqvist; Karin Gottvall; Lotte Berdiin Colmorn; Mika Gissler Journal: Acta Obstet Gynecol Scand Date: 2014-02 Impact factor: 3.636
Authors: Anna C Svensson; Sven Sandin; Sven Cnattingius; Marie Reilly; Yudi Pawitan; Christina M Hultman; Paul Lichtenstein Journal: Am J Epidemiol Date: 2009-10-23 Impact factor: 4.897
Authors: A Le Couteur; A Bailey; S Goode; A Pickles; S Robertson; I Gottesman; M Rutter Journal: J Child Psychol Psychiatry Date: 1996-10 Impact factor: 8.982
Authors: Linda S Lindström; Benjamin Yip; Paul Lichtenstein; Yudi Pawitan; Kamila Czene Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-08 Impact factor: 4.254
Authors: Paul Lichtenstein; Benjamin H Yip; Camilla Björk; Yudi Pawitan; Tyrone D Cannon; Patrick F Sullivan; Christina M Hultman Journal: Lancet Date: 2009-01-17 Impact factor: 79.321
Authors: Renee M Gardner; Brian K Lee; Cecilia Magnusson; Dheeraj Rai; Thomas Frisell; Håkan Karlsson; Selma Idring; Christina Dalman Journal: Int J Epidemiol Date: 2015-06-04 Impact factor: 7.196
Authors: Trent Gaugler; Lambertus Klei; Stephan J Sanders; Corneliu A Bodea; Arthur P Goldberg; Ann B Lee; Milind Mahajan; Dina Manaa; Yudi Pawitan; Jennifer Reichert; Stephan Ripke; Sven Sandin; Pamela Sklar; Oscar Svantesson; Abraham Reichenberg; Christina M Hultman; Bernie Devlin; Kathryn Roeder; Joseph D Buxbaum Journal: Nat Genet Date: 2014-07-20 Impact factor: 38.330
Authors: Cindy Skinner; Rini Pauly; Steven A Skinner; Richard J Schroer; Richard J Simensen; Harold A Taylor; Michael J Friez; Barbara R DuPont; Roger E Stevenson Journal: J Autism Dev Disord Date: 2021-02
Authors: Dan Bai; Natasha Marrus; Benjamin Hon Kei Yip; Abraham Reichenberg; John N Constantino; Sven Sandin Journal: Biol Psychiatry Date: 2020-04-02 Impact factor: 13.382
Authors: Anne B Arnett; Jennifer S Beighley; Evangeline C Kurtz-Nelson; Kendra Hoekzema; Tianyun Wang; Raphe A Bernier; Evan E Eichler Journal: Autism Res Date: 2020-09-12 Impact factor: 5.216
Authors: Mark J Taylor; Mina A Rosenqvist; Henrik Larsson; Christopher Gillberg; Brian M D'Onofrio; Paul Lichtenstein; Sebastian Lundström Journal: JAMA Psychiatry Date: 2020-09-01 Impact factor: 21.596
Authors: Jacqueline M Barkoski; Claire Philippat; Daniel Tancredi; Rebecca J Schmidt; Sally Ozonoff; Dana Boyd Barr; William Elms; Deborah H Bennett; Irva Hertz-Picciotto Journal: Environ Res Date: 2020-11-18 Impact factor: 6.498