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

Molly Losh,Gary E Martin,John Sideris,Michelle Lee,Thomas Wassink,Jessica Klusek,Sheila Barron

doi:10.1007/s10803-016-2996-x

Abstract

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents’ childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents’ childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of ASD genetic liability.

Highlights

Autism spectrum disorder (ASD) is a common and complex, genetically-based neurodevelopmental disorder (APA 2013; CDC 2014)
This study investigated developmental phenotypes potentially reflecting ASD genetic liability in parents, by making use of archival data from academic testing records over childhood, from a cohort of individuals who as adults would go on to have a child with ASD
hierarchical linear models (HLM) were run including random effects to account for the nesting within families

Summary

Introduction

Autism spectrum disorder (ASD) is a common and complex, genetically-based neurodevelopmental disorder (APA 2013; CDC 2014). ASD is highly familial and subclinical phenotypes that are qualitatively similar to core features of ASD have been repeatedly reported in a subset of relatives, which are believed to constitute endophenotypes (Bolton et al 1994; Landa et al 1991, 1992; Losh et al 2011; Murphy et al 2000; Piven et al 1997a, 1994). Endophenotypes are genetically influenced traits existing midstream between disease phenotype and underlying genetics (Gottesman and Gould 2003). They may manifest as a forme fruste of complex genetic disorders among unaffected relatives, as in ASD, where relatives often exhibit subclinical personality and language traits similar in quality to the core features of ASD but subtle in expression and not associated with functional impairment.

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