Abstract
Autism spectrum disorder (ASD) is defined by the triad of deficits in social interactions, deficits in communication, and repetitive behaviors. Common co-morbidities in syndromic forms of ASD include intellectual disability, seizures, and obesity. We asked whether very obese children with ASD had different behavioral, physical and genetic characteristics compared to children with ASD who were not obese. We found that very obese children with ASD had significantly poorer scores on standardized behavioral tests. Very obese boys with ASD had lower full scale IQ and increased impairments with respect to stereotypies, communication and social skills. Very obese girls with ASD had increased impairments with respect to irritability and oppositional defiant behavior. We identified genetic lesions in a subset of the children with ASD and obesity and attempted to identify enriched biological pathways. Our study demonstrates the value of identifying co-morbidities in children with ASD as we move forward towards understanding the biological processes that contribute to this complex disorder and prepare to design customized treatments that target the diverse genetic lesions present in individuals with ASD.
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Abbreviations
- ABC:
-
Aberrant Behavior Checklist
- ADI:
-
Autism Diagnostic Interview
- ASD:
-
Autism spectrum disorder
- BMI:
-
Body mass index,
- CBCL 6–18:
-
Child Behavior Checklist
- dnCNVs:
-
De novo copy number variants
- dnLGD:
-
De novo likely gene disrupting
- dnNSC:
-
De novo non-synonymous coding mutations
- ExAC:
-
Exome Aggregation Consortium
- FSIQ:
-
Full scale IQ
- GO:
-
Gene Ontology
- ID:
-
Intellectual disability
- LoF:
-
Loss of function
- PCP:
-
Planar cell polarity
- PWS:
-
Prader–Willi syndrome
- SSC:
-
Simons Simplex Collection
- VABS:
-
Vineland Adaptive Behavior Rating Scales
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Acknowledgements
We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, (A) Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, (B) Peterson, J. Piggot, (C) Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the SSC population dataset described in this study by applying at https://base.sfari.org. We are grateful to the Prader–Willi Association of Alberta for their donation in support of our research on autism spectrum disorders.
Funding
This work was supported by a Grant from the Simons Foundation for Autism Research (SFARIPA304216, to RW).
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HDC and RW analyzed and interpreted the mutation data and wrote the manuscript. Both authors read and approved the final manuscript.
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H. D. Cortes declares that he has no conflict of interest. R. Wevrick declares that she has no conflict of interest.
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“All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.” Use of SSC data from human subjects was approved by the Health Research Ethics Board-Biomedical Panel of the University of Alberta, Edmonton, Alberta Canada. This article does not contain any studies with animals performed by any of the authors.
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The data that support the findings of this study are available from the Simons Foundation but restrictions apply to the availability of these data, which were used under license for the current study. Data are however available from the authors upon reasonable request and with permission of the Simons Foundation.
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Cortes, H.D., Wevrick, R. Genetic analysis of very obese children with autism spectrum disorder. Mol Genet Genomics 293, 725–736 (2018). https://doi.org/10.1007/s00438-018-1418-5
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DOI: https://doi.org/10.1007/s00438-018-1418-5