TY - JOUR
T1 - Early behavioral indices of inherited liability to autism
AU - Constantino, John N.
N1 - Funding Information:
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number U54 HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University in St. Louis. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2018, International Pediatric Research Foundation, Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - OBJECTIVE: The observed heterogeneity of autism spectrum disorder (ASD)—and the diversity of rare germline mutations with which it has been associated—has been difficult to reconcile with knowledge of its pronounced heritability in the population. Methods: This article reviews and synthesizes recent family and developmental studies incorporating behavioral indices of inherited risk for ASD. Results: Autism may arise from critical combinations of early inherited neurobehavioral susceptibilities—some specific to autism, some not—each of which may be traceable to partially-independent sets of genetic variation. These susceptibilities and their respective genetic origins may not relate to the characterizing symptoms of autism (after it develops) in a straightforward way, and may account for “missing heritability” in molecular genetic studies. Conclusions: Within-individual aggregations of a finite set of early inherited neurobehavioral susceptibilities—each individually common in the population—may account for a significant share of the heritability of ASD. Comprehensive identification of these underlying traits my help elucidate specific early intervention targets in individual patients, especially if autism represents a developmental consequence of earlier-interacting susceptibilities. Scientific understanding of the early ontogeny of autism will benefit from epidemiologically-rigorous, genetically-informative studies of robust endophenotypic candidates whose inter-relationships in infancy are mapped and normed.
AB - OBJECTIVE: The observed heterogeneity of autism spectrum disorder (ASD)—and the diversity of rare germline mutations with which it has been associated—has been difficult to reconcile with knowledge of its pronounced heritability in the population. Methods: This article reviews and synthesizes recent family and developmental studies incorporating behavioral indices of inherited risk for ASD. Results: Autism may arise from critical combinations of early inherited neurobehavioral susceptibilities—some specific to autism, some not—each of which may be traceable to partially-independent sets of genetic variation. These susceptibilities and their respective genetic origins may not relate to the characterizing symptoms of autism (after it develops) in a straightforward way, and may account for “missing heritability” in molecular genetic studies. Conclusions: Within-individual aggregations of a finite set of early inherited neurobehavioral susceptibilities—each individually common in the population—may account for a significant share of the heritability of ASD. Comprehensive identification of these underlying traits my help elucidate specific early intervention targets in individual patients, especially if autism represents a developmental consequence of earlier-interacting susceptibilities. Scientific understanding of the early ontogeny of autism will benefit from epidemiologically-rigorous, genetically-informative studies of robust endophenotypic candidates whose inter-relationships in infancy are mapped and normed.
UR - http://www.scopus.com/inward/record.url?scp=85056139000&partnerID=8YFLogxK
U2 - 10.1038/s41390-018-0217-3
DO - 10.1038/s41390-018-0217-3
M3 - Review article
C2 - 30356093
AN - SCOPUS:85056139000
SN - 0031-3998
VL - 85
SP - 127
EP - 133
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -