Recurrence of Autism Spectrum Disorders in Full- and Half-Siblings and Trends Over Time

Abstract

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.

ASD Validity

“…Recurrence risk is the likelihood that a second child with ASD would be born in a family where a child has already been diagnosed with ASD. No consistent recurrence risk for ASD has been established, and rates have varied from 6 to 19 % (Grønborg et al 2013;Ozonoff et al 2011;Ronemus et al 2014;Rosti et al 2014;Werling and Geschwind 2013).…”

“…An example of varied genetic transmission was reported by Jiang et al (2013), who found multiple varied ASD inheritance patterns in just 16 families: 12 rare X-linked deleterious variants, 7 rare deleterious autosomal-dominant mutations, 13 deleterious missense mutations, and 15 de novo deleterious mutations. Another problem for recurrence rate determination was discovered by Grønborg et al (2013), who found increased ASD risk in maternal half-siblings, indicating that environmental factors unique to the mother's pregnancy history may contribute to ASD recurrence risk.…”

Considering Development in Developmental Disorders

“…Such "infant sibling" studies are especially important for understanding how autism emerges, because younger siblings of children with ASD are 5 times more likely to be diagnosed with ASD than the general population (Grønborg, Schendel, & Parner, 2013;Ozonoff et al, 2011). There has been a great deal of speculation about the role of brain size in ASD, and some data have suggested that toddlers who are later diagnosed with ASD have larger brains than those who are not (Hazlett et al, 2005(Hazlett et al, , 2012Schumann et al, 2010).…”

Advances in Genetic Diagnosis of Autism Spectrum Disorders

“…If multiple children (two or more) are affected, recurrence risk increases to about 33 % or more. Newer data suggest a recurrence risk of 7-19 % when one child is affected, and similar risk of 33 % or more when two or more children in a family are affected [67][68][69]. The ACMG guideline suggests using the lower risk estimates until the newer results have been replicated.…”