THE FAMILIAL RISK OF AUTISM

By S. Sandin, P. Lichtenstein, R. Kuja-Halkola, H. Larsson, C. Hultman, A. Reichenberg. Journal of the American Medical Association (JAMA), 2014

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Importance Autism Spectrum Disorders (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors, or shared or non-shared environment remains unresolved. Objective To provide estimates of familial aggregation of ASD. Design, Setting and Participants A population based cohort of all Swedish children born 1982–2007. We identified all twins, full siblings, maternal and paternal half siblings and cousin pairs and all diagnosis of ASD to 31-December-2009. Main Outcome Measure(s) The relative recurrence risk (RR) measure familial aggregation of disease. The RR is the relative risk of autism in an participant given a sibling or cousin has the diagnosis, compared with the risk in a participant with no diseased family member. We calculated RR for both ASD and Autistic Disorder (AD). We estimated how much of the probability of developing ASD can be related to genetic (additive and dominance) and environmental (shared and non-shared) factors. Results In the sample of 2,049,899 children, 14,516 obtained an ASD diagnosis of which 5,689 were AD. The ASD RR was estimated to 153.0 (95%CI 56.7–412.8; 27 vs 6,273 per 100,000 person-years) for monozygotic twins, 8.2 (95%CI 3.7–18.1; 55 vs 805 per 100,000 person-years) for dizygotic twins, 10.3 (95%CI 9.4–11.2; 49 vs 829 per 100,000 person-years) for full-siblings, 3.3 (95%CI 2.6–4.2; 94 vs 492 per 100,000 person-years) for maternal half siblings, 2.9 (95%CI: 2.2–3.7; 85 vs 371 per 100,000 person-years) for paternal half siblings, and 2.0 (95%CI: 1.8–2.2; 49 vs 155 per 100,000 person-years) for cousins. The RR pattern was similar for AD but of slightly higher magnitude. We found support for a disease etiology including only additive genetic and non-shared environmental effects. The ASD heritability was estimated to 0.50 (95%CI 0.44–0.55) and the AD heritability was estimated to 0.54 (95%CI 0.44–0.64). Conclusion and Relevance Among children born in Sweden, heritability of ASD and AD were estimated to be approximately 50%. For an individual, the risk of autism is increased 10 fold if a full sibling has the diagnosis and about 2 fold if a cousin has the diagnosis. These findings may inform counseling families with affected children.

Subfields: Clinical Psychology, Cognitive Neuroscience, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/8a80312d587014d076696015ecac44bf3b4d8c87

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Citations in the corpus

Advancing the understanding of autism disease mechanisms through genetics (2016, positive): “Firstly, recurrence of ASD in families implies a strong inherited genetic component 28,29 .”
Heritability of autism spectrum disorders: a meta‐analysis of twin studies (2015, background): “The meta-analysis results are in line with the results from the largest extended family population study (Sandin et al., 2014), (showing no effects of shared environment) as well as results from the only random population twin study, which did not need to rely on fixed threshold correction…”
The Changing Epidemiology of Autism Spectrum Disorders (2016, background): “Additionally, estimates of recurrence risk among siblings of autistic children range from 3% to 18% (71, 138, 155).”
Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation (2020, background): “Genetic factors play a role in ASD susceptibility, with siblings of patients with ASD carrying an increased risk of diagnosis when compared to population norms, and a much higher, although not absolute, concordance of autism diagnosis in monozygotic twins (42-44).”
Sex/Gender Differences and Autism: Setting the Scene for Future Research (2015, background): “100-103 Additional supportive evidence comes from multiplex autism families, where affected males from families with affected females show more RRBI (but not social – communication symptoms) than affected males from families without affected females.”