Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months.

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TitleQuantitative trait variation in ASD probands and toddler sibling outcomes at 24 months.
Publication TypeJournal Article
Year of Publication2020
AuthorsGirault, JB, Swanson, MR, Meera, SS, Grzadzinski, RL, Shen, MD, Burrows, CA, Wolff, JJ, Pandey, J, St John, T, Estes, A, Zwaigenbaum, L, Botteron, KN, Hazlett, HC, Dager, SR, Schultz, RT, Constantino, JN, Piven, J
Corporate AuthorsIBIS Network
JournalJ Neurodev Disord
Date Published2020 02 05

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.

Alternate JournalJ Neurodev Disord
PubMed ID32024459
PubMed Central IDPMC7003330
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
T32 HD040127 / HD / NICHD NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States
R01 MH118362 / MH / NIMH NIH HHS / United States
P30-HD003110 / NH / NIH HHS / United States
R01 HD055741 / HD / NICHD NIH HHS / United States