Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study

Background: Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. To date, investigations of ASD endophenotypes in parents have necessarily been restricted to assessments administered in adulthood, when status as a parent of a child with ASD is determined. This leaves unexamined a large swath of time during which ASD endophenotypes are likely to first arise, and might be most profitably studied for clues into underlying biology. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents’ childhood academic development over the school-age period, using archival standardized testing records from kindergarten-high school. Parents’ childhood developmental profiles were examined in relationship to endophenotypes in adulthood, and ASD symptom expression in the next generation.

 

Objectives: To identify developmental endophenotypes in parents of individuals with ASD using archival testing data from childhood.

Methods: A cohort of 139 parents and their children with ASD, and 28 adult controls participated. Archival records of standardized test performance in the domains of language, reading, and math were examined from grades K-12. Additionally, a battery of cognitive, language and personality measures were administered to parents. ASD symptoms in children were measured using the gold-standard diagnostic measures for children with ASD. Parents’ performance over time was examined relative to controls as well as in relationship to clinical-behavioral endophenotypes in adulthood, and their children’s ASD symptoms.

 

Results: Subtle differences were observed in the language domain, with the ASD parent group showing lower language skills than controls overall. Additionally, relatively slower development of language and math skills, and a fractionated, or uneven rate of development across domains in the ASD parent group predicted ASD endophenotypes in adulthood for parents, and increased symptom severity in their children diagnosed with ASD.

 

Conclusions: Results identified developmental profiles in parents of individuals with ASD that are related to endophenotypes measureable in adulthood among parents, and ASD symptom severity in parents’ offspring. Evidence of such early expression of genetic liability, in patterns of academic performance across major curricular domains of language, reading, and math (and perhaps language in particular), a generation removed from affected individuals, may help to advance neural and genetic research by stratifying individuals and families to examine biological factors differentially associated with genetically meaningful developmental phenotypes in parents.