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Nat Commun. 2019 Dec 5;10(1):5519. doi: 10.1038/s41467-019-13380-2.

Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Author information

1
The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
2
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
3
Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Department of Women's and Children's Health, Stockholm, Sweden.
4
Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden.
5
Autism Research Centre, Bloorview Research Institute and University of Toronto, Toronto, ON, Canada.
6
Autism Research Centre, IWK Health Centre and Dalhousie University, Halifax, NS, Canada.
7
Department of Psychology, UC San Diego, La Jolla, CA, USA.
8
Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD, USA.
9
Department of Psychology, University of Miami, Coral Gables, FL, USA.
10
MIND Institute, Department of Psychiatry, UC Davis, Davis, CA, USA.
11
Department of Psychology, University of Washington, Seattle, WA, USA.
12
Vanderbilt Kennedy Center Treatment and Research Institute for Autism Spectrum Disorders, Vanderbilt Kennedy Centre, Nashville, TN, USA.
13
Autism Research Centre, University of Alberta, Edmonton, AB, Canada.
14
The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada. stephen.scherer@sickkids.ca.
15
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. stephen.scherer@sickkids.ca.
16
McLaughlin Centre, University of Toronto, Toronto, ON, Canada. stephen.scherer@sickkids.ca.

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.

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