Behavioral predictors of autism recurrence are genetically independent and influence social reciprocity: evidence that polygenic ASD risk is mediated by separable elements of developmental liability

• Type of Material: Article
• Authors: Alexa Pohl, Washington University; Warren Jones, Emory University; Natasha Marrus, Washington University; Yi Zhang, Washington University; Ami Klin, Emory University; John N. Constantino, Washington University
• Language: English
• Date: 2019-08-22
• Publisher: Springer Nature [academic journals on nature.com]: Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41398-019-0545-z
• Title of Journal or Parent Work: Translational Psychiatry
• ISSN: 2158-3188
• Volume: 9
• Issue: 1
• Start Page: 202
• End Page: 202
• Grant/Funding Information: This research was supported by grants from the National Institute of Child Health and Human Development, HD068479 (J.N.C.); and U54 HD087011 (Intellectual and Developmental Disabilities Research Center at Washington University, J.N.C., principal investigator); and by the National Institute of Mental Health, MH100019 (N.M.).
• Keywords: Life Sciences & Biomedicine; RESPONSIVENESS; TRAITS; TRANSMISSION; Psychiatry; MOTOR; Science & Technology; INFANTS
• Research Categories: Health Sciences, Mental Health; Psychology, Developmental

Abstract

The preponderance of causal influence on total population attributable risk for autism is polygenic in nature, but it is not known how such liability engenders the development of the syndrome. In 348 epidemiologically ascertained toddler twins, we explored associations between autistic traits and three robust, highly heritable predictors of familial autism recurrence: variation in attention, motor coordination, and parental autistic trait burden. We observed that these predictors—despite collectively accounting for over one third of variance in clinical recurrence—are genetically independent in early childhood, and jointly account for a comparable share of inherited influence on early reciprocal social behavior in the general population. Thus, combinations of what are otherwise discrete, inherited behavioral liabilities—some not specific to autism—appear to jointly mediate common genetic risk for autism. Linking genetic variants and neural signatures to these independent traits prior to the onset of the development of autism will enhance understanding of mechanisms of causation in familial autistic syndromes. Moreover, ongoing biomarker discovery efforts will benefit from controlling for the effects of these common liabilities, which aggregate in individuals with autism but are also continuously distributed in “controls”. Finally, early inherited liabilities that participate in the early ontogeny of autistic syndromes represent parsimonious intervention targets for polygenic forms of the condition, and represent candidate trans-diagnostic endophenotypes of potential relevance to a diversity of neuropsychiatric syndromes.