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

doi:10.1016/j.jaac.2018.11.017

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 journal › Article › peer-review

63 Scopus citations

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 language	English
Pages (from-to)	866-875
Number of pages	10
Journal	Journal of the American Academy of Child and Adolescent Psychiatry
Volume	58
Issue number	9
DOIs	https://doi.org/10.1016/j.jaac.2018.11.017
State	Published - Sep 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 American Academy of Child and Adolescent Psychiatry

Funding

This study was supported by grant HD073978 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. The funding did not play any role in study design; collection, analysis, or interpretation of data; writing of the report; or the decision to submit the article for publication. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the California Department of Public Health.Disclosure: Dr. Schendel has received support by an unrestricted grant from the Lundbeck Foundation (iPSYCH). Dr. Sandin has received support by grants from the Beatrice and Samuel A. Seaver Foundation as a Seaver Fellow. Dr. Buxbaum has received support by a grant from the National Institute of Mental Health (MH097849). Drs. Hansen, Francis, Windham, Bresnahan, Levine, Reichenberg, Gissler, Kodesh, Yip, Leonard, Hultman, Sourander, Glasson, Wong, and Parner and Messrs. Bai and Öberg report no biomedical financial interests or potential conflicts of interest. This study was supported by grant HD073978 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. The funding did not play any role in study design; collection, analysis, or interpretation of data; writing of the report; or the decision to submit the article for publication. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the California Department of Public Health. Disclosure: Dr. Schendel has received support by an unrestricted grant from the Lundbeck Foundation (iPSYCH). Dr. Sandin has received support by grants from the Beatrice and Samuel A. Seaver Foundation as a Seaver Fellow. Dr. Buxbaum has received support by a grant from the National Institute of Mental Health (MH097849). Drs. Hansen, Francis, Windham, Bresnahan, Levine, Reichenberg, Gissler, Kodesh, Yip, Leonard, Hultman, Sourander, Glasson, Wong, and Parner and Messrs. Bai and Öberg report no biomedical financial interests or potential conflicts of interest.

Funders	Funder number
National Institute of Mental Health	MH097849
National Institute of Neurological Disorders and Stroke
National Institute of Environmental Health Sciences
National Institute of Child Health and Human Development	U01HD073978
California Department of Public Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Beatrice and Samuel A. Seaver Foundation
Lundbeckfonden

Keywords

autism
familial risk
longitudinal
multinational
recurrence

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jaac.2018.11.017

Cite this

Hansen, S. N., Schendel, D. E., Francis, R. W., Windham, G. C., Bresnahan, M., Levine, S. Z., Reichenberg, A., Gissler, M., Kodesh, A., Bai, D., Yip, B. H. K., Leonard, H., Sandin, S., Buxbaum, J. D., Hultman, C., Sourander, A., Glasson, E. J., Wong, K., Öberg, R., & 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

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

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.",

keywords = "autism, familial risk, longitudinal, multinational, recurrence",

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

note = "Publisher Copyright: {\textcopyright} 2019 American Academy of Child and Adolescent Psychiatry",

year = "2019",

month = sep,

doi = "10.1016/j.jaac.2018.11.017",

language = "אנגלית",

volume = "58",

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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

TY - JOUR

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

Y1 - 2019/9

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.

KW - autism

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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