Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study

Stefan N. Hansen, Diana E. Schendel, Richard W. Francis, Gayle C. Windham, Michaeline Bresnahan, Stephen Z. Levine, Abraham Reichenberg, Mika Gissler, Arad Kodesh, Dan Bai, Benjamin Hon Kei Yip, H. Leonard, Sven Sandin, Joseph D. Buxbaum, Christina Hultman, A. Sourander, Emma J. Glasson, Kingsley Wong, Rikard Öberg, Erik T. Parner

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)866-875
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume58
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

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Autistic Disorder
Recurrence
Population
Autism Spectrum Disorder
Parturition
Western Australia
Israel
Denmark
Finland
Sweden
Cohort Studies

Cite this

Hansen, S. N., Schendel, D. E., Francis, R. W., Windham, G. C., Bresnahan, M., Levine, S. Z., ... Parner, E. T. (2019). Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study. Journal of the American Academy of Child and Adolescent Psychiatry, 58(9), 866-875. https://doi.org/10.1016/j.jaac.2018.11.017
Hansen, Stefan N. ; Schendel, Diana E. ; Francis, Richard W. ; Windham, Gayle C. ; Bresnahan, Michaeline ; Levine, Stephen Z. ; Reichenberg, Abraham ; Gissler, Mika ; Kodesh, Arad ; Bai, Dan ; Yip, Benjamin Hon Kei ; Leonard, H. ; Sandin, Sven ; Buxbaum, Joseph D. ; Hultman, Christina ; Sourander, A. ; Glasson, Emma J. ; Wong, Kingsley ; Öberg, Rikard ; Parner, Erik T. / Recurrence Risk of Autism in Siblings and Cousins : A Multinational, Population-Based Study. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2019 ; Vol. 58, No. 9. pp. 866-875.
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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.",
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Hansen, SN, Schendel, DE, Francis, RW, Windham, GC, Bresnahan, M, Levine, SZ, Reichenberg, A, Gissler, M, Kodesh, A, Bai, D, Yip, BHK, Leonard, H, Sandin, S, Buxbaum, JD, Hultman, C, Sourander, A, Glasson, EJ, Wong, K, Öberg, R & Parner, ET 2019, 'Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study' Journal of the American Academy of Child and Adolescent Psychiatry, vol. 58, no. 9, pp. 866-875. https://doi.org/10.1016/j.jaac.2018.11.017

Recurrence Risk of Autism in Siblings and Cousins : A Multinational, Population-Based Study. / Hansen, Stefan N.; Schendel, Diana E.; Francis, Richard W.; Windham, Gayle C.; Bresnahan, Michaeline; Levine, Stephen Z.; Reichenberg, Abraham; Gissler, Mika; Kodesh, Arad; Bai, Dan; Yip, Benjamin Hon Kei; Leonard, H.; Sandin, Sven; Buxbaum, Joseph D.; Hultman, Christina; Sourander, A.; Glasson, Emma J.; Wong, Kingsley; Öberg, Rikard; Parner, Erik T.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 58, No. 9, 01.09.2019, p. 866-875.

Research output: Contribution to journalArticle

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T1 - Recurrence Risk of Autism in Siblings and Cousins

T2 - A Multinational, Population-Based Study

AU - Hansen, Stefan N.

AU - Schendel, Diana E.

AU - Francis, Richard W.

AU - Windham, Gayle C.

AU - Bresnahan, Michaeline

AU - Levine, Stephen Z.

AU - Reichenberg, Abraham

AU - Gissler, Mika

AU - Kodesh, Arad

AU - Bai, Dan

AU - Yip, Benjamin Hon Kei

AU - Leonard, H.

AU - Sandin, Sven

AU - Buxbaum, Joseph D.

AU - Hultman, Christina

AU - Sourander, A.

AU - Glasson, Emma J.

AU - Wong, Kingsley

AU - Öberg, Rikard

AU - Parner, Erik T.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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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KW - familial risk

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JF - Journal of the American Academy of Child & Adolescent Psychiatry

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