An integrated analysis of rare CNV and exome variation in Autism Spectrum Disorder using the Infinium PsychArray.
Autism Spectrum Disorder
/ genetics
DNA Copy Number Variations
Exome
Family Health
Female
Gene Deletion
Gene Duplication
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Heterozygote
Humans
Italy
/ epidemiology
Linkage Disequilibrium
Male
Oligonucleotide Array Sequence Analysis
Parents
Pedigree
Polymorphism, Single Nucleotide
Risk
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 02 2020
21 02 2020
Historique:
received:
05
09
2019
accepted:
19
01
2020
entrez:
22
2
2020
pubmed:
23
2
2020
medline:
31
12
2020
Statut:
epublish
Résumé
Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex and heterogeneous genetic etiology. While a proportion of ASD risk is attributable to common variants, rare copy-number variants (CNVs) and protein-disrupting single-nucleotide variants (SNVs) have been shown to significantly contribute to ASD etiology. We analyzed a homogeneous cohort of 127 ASD Italian families genotyped with the Illumina PsychArray, to perform an integrated analysis of CNVs and SNVs and to assess their contribution to ASD risk. We observed a higher burden of rare CNVs, especially deletions, in ASD individuals versus unaffected controls. Furthermore, we identified a significant enrichment of rare CNVs intersecting ASD candidate genes reported in the SFARI database. Family-based analysis of rare SNVs genotyped by the PsychArray also indicated an increased transmission of rare SNV variants from heterozygous parents to probands, supporting a multigenic model of ASD risk with significant contributions of both variant types. Moreover, our study reinforced the evidence for a significant role of VPS13B, WWOX, CNTNAP2, RBFOX1, MACROD2, APBA2, PARK2, GPHN, and RNF113A genes in ASD susceptibility. Finally, we showed that the PsychArray, besides providing useful genotyping data in psychiatric disorders, is a valuable and cost-efficient tool for genic CNV detection, down to 10 kb.
Identifiants
pubmed: 32081867
doi: 10.1038/s41598-020-59922-3
pii: 10.1038/s41598-020-59922-3
pmc: PMC7035424
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3198Références
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