Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months
Posted on 2020-02-06 - 04:55
Abstract Background Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. Methods Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. Results Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9–18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). Conclusions Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.
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Girault, Jessica; Swanson, Meghan; Meera, Shoba; Grzadzinski, Rebecca; Shen, Mark; Burrows, Catherine; et al. (2020). Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4845678.v1
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AUTHORS (17)
JG
Jessica Girault
MS
Meghan Swanson
SM
Shoba Meera
RG
Rebecca Grzadzinski
MS
Mark Shen
CB
Catherine Burrows
JW
Jason Wolff
JP
Juhi Pandey
TJ
Tanya John
AE
Annette Estes
LZ
Lonnie Zwaigenbaum
KB
Kelly Botteron
HH
Heather Hazlett
SD
Stephen Dager
RS
Robert Schultz
JC
John Constantino
JP
Joseph Piven