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

L. D’Abate; S. Walker; R. K.C. Yuen; K. Tammimies; J. A. Buchanan; R. W. Davies; B. Thiruvahindrapuram; J. Wei; J. Brian; S. E. Bryson; K. Dobkins; J. Howe; R. Landa; J. Leef; D. Messinger; S. Ozonoff; I. M. Smith; W. L. Stone; Z. E. Warren; G. Young; L. Zwaigenbaum; S. W. Scherer

doi:10.1038/s41467-019-13380-2

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

L. D’Abate, S. Walker, R. K.C. Yuen, K. Tammimies, J. A. Buchanan, R. W. Davies, B. Thiruvahindrapuram, J. Wei, J. Brian, S. E. Bryson, K. Dobkins, J. Howe, R. Landa, J. Leef, D. Messinger, S. Ozonoff, I. M. Smith, W. L. Stone, Z. E. Warren, G. YoungL. Zwaigenbaum, S. W. Scherer

Psychology

Research output: Contribution to journal › Article

2 Scopus citations

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.

Original language	English (US)
Article number	5519
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13380-2
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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D’Abate, L., Walker, S., Yuen, R. K. C., Tammimies, K., Buchanan, J. A., Davies, R. W., Thiruvahindrapuram, B., Wei, J., Brian, J., Bryson, S. E., Dobkins, K., Howe, J., Landa, R., Leef, J., Messinger, D., Ozonoff, S., Smith, I. M., Stone, W. L., Warren, Z. E., ... Scherer, S. W. (2019). Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders. Nature communications, 10(1), [5519]. https://doi.org/10.1038/s41467-019-13380-2

Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders. / D’Abate, L.; Walker, S.; Yuen, R. K.C.; Tammimies, K.; Buchanan, J. A.; Davies, R. W.; Thiruvahindrapuram, B.; Wei, J.; Brian, J.; Bryson, S. E.; Dobkins, K.; Howe, J.; Landa, R.; Leef, J.; Messinger, D.; Ozonoff, S.; Smith, I. M.; Stone, W. L.; Warren, Z. E.; Young, G.; Zwaigenbaum, L.; Scherer, S. W.

In: Nature communications, Vol. 10, No. 1, 5519, 01.12.2019.

Research output: Contribution to journal › Article

D’Abate, L, Walker, S, Yuen, RKC, Tammimies, K, Buchanan, JA, Davies, RW, Thiruvahindrapuram, B, Wei, J, Brian, J, Bryson, SE, Dobkins, K, Howe, J, Landa, R, Leef, J, Messinger, D, Ozonoff, S, Smith, IM, Stone, WL, Warren, ZE, Young, G, Zwaigenbaum, L & Scherer, SW 2019, 'Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders', Nature communications, vol. 10, no. 1, 5519. https://doi.org/10.1038/s41467-019-13380-2

D’Abate, L. ; Walker, S. ; Yuen, R. K.C. ; Tammimies, K. ; Buchanan, J. A. ; Davies, R. W. ; Thiruvahindrapuram, B. ; Wei, J. ; Brian, J. ; Bryson, S. E. ; Dobkins, K. ; Howe, J. ; Landa, R. ; Leef, J. ; Messinger, D. ; Ozonoff, S. ; Smith, I. M. ; Stone, W. L. ; Warren, Z. E. ; Young, G. ; Zwaigenbaum, L. ; Scherer, S. W. / Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders. In: Nature communications. 2019 ; Vol. 10, No. 1.

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