Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders
| Autor: | Jennifer L. Howe, Lia D’Abate, Zachary Warren, Stephen W. Scherer, Karen R. Dobkins, Ryan K. C. Yuen, John Wei, Janet A. Buchanan, Gregory S. Young, Kristiina Tammimies, Wendy L. Stone, Susan Walker, Bhooma Thiruvahindrapuram, Jessica Brian, S. E. Bryson, J. Leef, Robert W. Davies, Rebecca Landa, Sally J Ozonoff, Lonnie Zwaigenbaum, Isabel M. Smith, Daniel S. Messinger |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Pediatrics Microarray genetic structures Autism Spectrum Disorder Autism General Physics and Astronomy 0302 clinical medicine Risk Factors 2.1 Biological and endogenous factors Recurrence prediction Copy-number variation Aetiology lcsh:Science Child Pediatric Multidisciplinary Genome Genomics Autism spectrum disorders Pedigree Mental Health Phenotype Autism spectrum disorder Child Preschool Female Human medicine.medical_specialty DNA Copy Number Variations Intellectual and Developmental Disabilities (IDD) Science Predictive markers behavioral disciplines and activities Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Clinical Research mental disorders Genetics medicine Humans Genetic Predisposition to Disease Genetic Testing Sibling Preschool Family Health Genome Human business.industry Siblings Human Genome Rare variants General Chemistry medicine.disease Human genetics Brain Disorders 030104 developmental biology Polygenic risk score lcsh:Q Structural variation business 030217 neurology & neurosurgery |
| Zdroj: | Nature communications, vol 10, iss 1 Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) Nature Communications |
| Popis: | 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. Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort. |
| Databáze: | OpenAIRE |
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