Recurrence of Autism Spectrum Disorders in Full- and Half-Siblings and Trends Over Time: A Population-Based Cohort Study
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IMPORTANCE: To date, this is the first population-based study to examine the recurrence risk for autism spectrum disorders (ASDs), including time trends, and the first study to consider the ASDs recurrence risk for full- and half-siblings. OBJECTIVES: To estimate the relative recurrence risk for ASDs in a Danish population, including recurrence in full- and half-siblings, and to examine time trends in ASDs relative to the recurrence risk. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study in Denmark. All children (about 1.5 million) born in Denmark between January 1, 1980, and December 31, 2004, were identified and followed up to December 31, 2010. We identified a maternal sibling subcohort derived from mothers with at least 2 children and a paternal sibling subcohort derived from fathers with at least 2 children. EXPOSURES: Children having an older sibling with ASDs are compared with children not having an older sibling with ASDs. MAIN OUTCOMES AND MEASURES: The adjusted hazard ratio for ASDs among children having an older sibling with ASDs compared with children not having an older sibling with ASDs. RESULTS The overall relative recurrence risk for ASDs was 6.9 (95% CI, 6.1-7.8), and it did not change significantly over time; similar risks were observed in maternal and paternal full-siblings. The relative recurrence risks were 2.4 (95% CI, 1.4-4.1) for maternal half-siblings and 1.5 (95% CI, 0.7-3.4) for paternal half-siblings. CONCLUSIONS AND RELEVANCE: Our population-based recurrence risk estimate is lower than the recently reported estimates from clinical samples. Our results demonstrate no time trend in the ASDs recurrence risk as seen in the ASDs prevalence. The difference in the recurrence risk between full- and half-siblings supports the role of genetics in ASDs, while the significant recurrence risk in maternal half-siblings may support the role of factors associated with pregnancy and the maternal intrauterine environment in ASDs.
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Only few earlier studies have had the possibility to calculate the relative recurrence risk.
“Only few earlier studies have had the possibility to calculate the RR8,27,28.”
From The Familial Risk of Autism (2014) · cites this paper as [27]
Differences in the prevalence of ASD among males and females are among the most well-documented features of the disorder, but these sex differences vary by sample and ascertainment procedure.
“Differences in the prevalence of ASD among males and females are among the most well-documented features of the disorder, but these sex differences vary by sample and ascertainment procedure [3, 8, 33].”
From Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study (2015) · cites this paper as [33]
The liability threshold model helps explain the relatively high sibling risk, the greater mutational burden in ASD probands than unaffected siblings, etiological heterogeneity within affected sibling pairs, and variable expressivity of certain loci.
“The model helps in the understanding of the relatively high risk for siblings of individuals diagnosed with ASD (13,46), the increased mutational burden in ASD probands compared with their unaffected siblings (22,28), etiological heterogeneity even within pairs of affected siblings (47,48) and, as we shall discuss further, the variable expressivity of certain loci (49,50) (Fig. 1).”
From Genetics and genomics of autism spectrum disorder: embracing complexity (2015) · cites this paper as [46]
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- Authors
- Grønborg, T. K., Schendel, D. E., & Parner, E. T.
- Affiliations
- Aarhus University (DK)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Grønborg, Therese K.
- Venue
- JAMA Pediatrics
- Publisher
- American Medical Association (AMA)
- Published
- 2013-10-01
- Volume
- 167
- Issue
- 10
- Pages
- 947
- ISSN
- 1072-4710 (ISSN-L)
- 2168-6203
- PMC
- PMC4610344
- OpenAlex
- W2150648630
- Cited by
- 180
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 21 · 2017: 15 · 2016: 24 · 2015: 25 · 2014: 22 · 2013: 2
- FWCI
- 13.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Pediatrics and Adolescent Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CC999999)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Clinical Psychology › Family and Disability Support Research
- Keywords
- autism spectrum disorder, recurrence risk, siblings, full siblings, half-siblings, genetic risk, intrauterine environment, pregnancy factors, temporal trends
- MeSH terms
- Child, Child Development Disorders, Pervasive, Denmark, Female, Humans, Male, Recurrence, Registries, Risk, Cohort Studies, Prevalence, Proportional Hazards Models, Siblings
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