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Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder

Published online by Cambridge University Press:  09 November 2020

Natasha Marrus ,
Julia D. Grant ,
Brooke Harris-Olenak ,
Jordan Albright ,
Drew Bolster ,
Jon Randolph Haber ,
Theodore Jacob ,
Yi Zhang ,
Andrew C. Heath  and
Arpana Agrawal
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Natasha Marrus*
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Julia D. Grant
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA Department of Psychology, Maryville University of St. Louis, St. Louis, MO, USA
Brooke Harris-Olenak
Affiliation:
Kaiser Permanente San Jose, San Jose, CA, USA
Jordan Albright
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Drew Bolster
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Jon Randolph Haber
Affiliation:
Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, USA
Theodore Jacob
Affiliation:
Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, USA
Yi Zhang
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Andrew C. Heath
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Arpana Agrawal
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
John N. Constantino
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Jed T. Elison
Affiliation:
Institute of Child Development, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Anne L. Glowinski
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
*
Author for Correspondence: Natasha Marrus, MD, PhD, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Washington University School of Medicine, 660 South Euclid, Box 8504, St. Louis, MO63110, USA; E-mail: natasha@wustl.edu
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Abstract

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Keywords

quantitative autistic traitsreciprocal social behaviortoddlerstwinsvrRSB
Type
Special Section Articles
Information
Development and Psychopathology , Volume 32 , Special Issue 4: Conceptualizing and Interrogating Autism Spectrum Disorder from a Developmental Psychopathology Framework , October 2020 , pp. 1190 - 1205
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

†

Deceased August 22, 2016

*

Senior authors who contributed equally to the development of this manuscript

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