Stefan N Hansen1, Diana E Schendel2, Richard W Francis3, Gayle C Windham4, Michaeline Bresnahan5, Stephen Z Levine6, Abraham Reichenberg7, Mika Gissler8, Arad Kodesh9, Dan Bai10, Benjamin Hon Kei Yip10, Helen Leonard3, Sven Sandin11, Joseph D Buxbaum7, Christina Hultman12, Andre Sourander13, Emma J Glasson3, Kingsley Wong3, Rikard Öberg12, Erik T Parner14. 1. Aarhus University, Aarhus, Denmark. Electronic address: stefanh@ph.au.dk. 2. Aarhus University, Aarhus, Denmark; Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, National Centre for Register-based Research, Aarhus University. 3. Telethon Kids Institute, The University of Western Australia, Perth, Australia. 4. Environmental Health Investigations Branch, California Department of Public Health, Richmond, CA. 5. Columbia University, Mailman School of Public Health, New York, NY; New York State Psychiatric Institute, New York, NY. 6. University of Haifa, Haifa, Israel. 7. Icahn School of Medicine at Mount Sinai, New York, NY; Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY. 8. Division of Family Medicine, Karolinska Institutet; the University of Turku, Research Centre for Child Psychiatry, Turku, Finland; THL National Institute for Health and Welfare, Information Services Department, Helsinki, Finland. 9. University of Haifa, Haifa, Israel; Meuhedet Health Services, Tel Aviv, Israel. 10. The Chinese University of Hong Kong, the Jockey Club of School of Public Health and Primary Care, Division of Family Medicine, Hong Kong. 11. Icahn School of Medicine at Mount Sinai, New York, NY; Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY; Karolinska Institutet, Stockholm, Sweden. 12. Karolinska Institutet, Stockholm, Sweden. 13. Turku University and Turku University Hospital. 14. Aarhus University, Aarhus, Denmark.
Abstract
OBJECTIVE: Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex. METHOD: This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and Western Australia followed through 2011 to 2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their ASD diagnosis (outcome). The relative recurrence risk was estimated for different sibling and cousin pairs, for each site separately and combined, and by sex. RESULTS: During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases of childhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared with the risk in unaffected families, there was an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of CA following an older sibling with CA. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrence risk by sex. CONCLUSION: The present estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in the context of other families in their population. The observed variation by sex underlines the need to deepen the understanding of factors influencing ASD familial risk.
OBJECTIVE: Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex. METHOD: This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and Western Australia followed through 2011 to 2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their ASD diagnosis (outcome). The relative recurrence risk was estimated for different sibling and cousin pairs, for each site separately and combined, and by sex. RESULTS: During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases of childhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared with the risk in unaffected families, there was an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of CA following an older sibling with CA. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrence risk by sex. CONCLUSION: The present estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in the context of other families in their population. The observed variation by sex underlines the need to deepen the understanding of factors influencing ASD familial risk.
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