Abstract

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.

Details

Title
Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders
Author
L D’Abate 1 ; Walker, S 2 ; Yuen, R K C 1   VIAFID ORCID Logo  ; Tammimies, K 3   VIAFID ORCID Logo  ; Buchanan, J A 2 ; Davies, R W 2 ; Thiruvahindrapuram, B 2 ; Wei, J 2 ; Brian, J 4 ; Bryson, S E 5 ; Dobkins, K 6 ; Howe, J 2 ; Landa, R 7 ; Leef, J 4 ; Messinger, D 8 ; Ozonoff, S 9 ; Smith, I M 5 ; Stone, W L 10 ; Warren, Z E 11 ; Young, G 9 ; Zwaigenbaum, L 12 ; Scherer, S W 13 

 The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada 
 The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada 
 The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Department of Women’s and Children’s Health, Stockholm, Sweden; Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden 
 Autism Research Centre, Bloorview Research Institute and University of Toronto, Toronto, ON, Canada 
 Autism Research Centre, IWK Health Centre and Dalhousie University, Halifax, NS, Canada 
 Department of Psychology, UC San Diego, La Jolla, CA, USA 
 Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD, USA 
 Department of Psychology, University of Miami, Coral Gables, FL, USA 
 MIND Institute, Department of Psychiatry, UC Davis, Davis, CA, USA 
10  Department of Psychology, University of Washington, Seattle, WA, USA 
11  Vanderbilt Kennedy Center Treatment and Research Institute for Autism Spectrum Disorders, Vanderbilt Kennedy Centre, Nashville, TN, USA 
12  Autism Research Centre, University of Alberta, Edmonton, AB, Canada 
13  The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; McLaughlin Centre, University of Toronto, Toronto, ON, Canada 
Pages
1-9
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2321622518
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.