Background: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. Methods: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Results: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Conclusions: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.
Bibliographical noteFunding Information:
This study was supported by National Institutes of Health Autism Center of Excellence R01 grant (National Institute of Child Health and Human Development, #HD055741 to J.P.), Autism Speaks (#6020 to J.P.), the Simons Foundation (grant number #140209 to J.P.), the National Institute of Mental Health (K08 MH112891 to N.M.), the Intellectual and Developmental Disabilities Research Centers at Washington University (National Institutes of Health/National Institute of Child Health and Human Development U54 HD087011 to J.N.C.). Children's Hospital of Pennsylvania/University of Pennsylvania (National Institutes of Health/National Institute of Child Health and Human Development U54 HD086984 to R.T.S.), and the University of North Carolina (National Institutes of Health/National Institute of Child Health and Human Development U54 HD079124 to J.P.).
© 2018 The Author(s).
- Autism spectrum disorder
- Infant sibling