@article{7937c20620b34b4d93f9d0a3948a34a6,
title = "Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders",
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.",
author = "L. D{\textquoteright}Abate and S. Walker and Yuen, {R. K.C.} and K. Tammimies and Buchanan, {J. A.} and Davies, {R. W.} and B. Thiruvahindrapuram and J. Wei and J. Brian and Bryson, {S. E.} and K. Dobkins and J. Howe and R. Landa and J. Leef and D. Messinger and S. Ozonoff and Smith, {I. M.} and Stone, {W. L.} and Warren, {Z. E.} and G. Young and L. Zwaigenbaum and Scherer, {S. W.}",
note = "Funding Information: We would like to thank the families who took part in this study, and the affiliated clinicians and research staff who assisted in recruitment and clinical evaluations of the participants. The Center for Applied Genomics provided technical and conceptual support in the form of genotyping, sequencing, CNV calling and data processing. This study was funded jointly by Autism Speaks, Autism Speaks Canada, the Simons Foundation Autism Research Initiative, Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation (CFI), The Hospital for Sick Children Foundation, Genome Canada/Ontario Genomics, Kids Brain Health Network, Canadian Institutes for Advanced Research (CIFAR), Ontario Brain Institute, Women and Children{\textquoteright}s Health Research Institute at the University of Alberta, the Government of Ontario, and the University of Toronto McLaughlin Center at the University of Toronto. The authors wish to acknowledge the resources of Autism Speaks, MSSNG (www.mss.ng), as well as the generosity of the donors who supported this program. We also thank the participating families for their time and contributions to this database. Data collection was supported in part in the USA by National Institutes of Health (NIH) R01 HD047417 (D.M.), NIH R01 HD057284 (W.L.S., D.M.) and NIMH R01 MH059630 (R.L.). L.D.A. is funded by the Research Training Competition Doctoral Scholarships awarded by the Hospital for Sick Children. R.K.C.Y. is funded by the CIHR Postdoctoral Fellowship, NARSAD Young Investigator Award and Thrasher Early Career Award. L.Z holds the Stollery Children{\textquoteright}s Foundation Chair in Autism. S.W.S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-13380-2",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}