The phenotypic manifestations of rare genic CNVs in autism spectrum disorder

• DOI: 10.1038/mp.2014.150
• Publication Date: 2014-11-25T08:56:13Z
• Authors: A K Merikangas; R Segurado; E A Heron; R J L Anney; A D Paterson; E H Cook; D Pinto; S W Scherer; P Szatmari; M Gill; A P Corvin; L Gallagher
• Keywords: Heritability of autism

Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on diagnosis ASD. There is limited understanding impact CNVs 'sub-phenotypes' The objective paper to evaluate associations in differentially brain expressed (DBE) genes or previously implicated ASD/intellectual disability (ASD/ID) specific sub-phenotypes sample consisted 1590 cases European ancestry from Genome Project (AGP) with a an ASD at least one rare CNV impacting any gene core set phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) adaptive function, as well paternal maternal age. Classification analyses using non-parametric recursive partitioning method (random forests) were employed define sets characteristics that best classify CNV-defined groups. was substantial variation classification accuracy two genes. variables verbal IQ ASD/ID genes, age birth DBE function de novo CNVs. list primarily associated communication domains, whereas related broader manifestations function. To our knowledge, first study examine genome-wide This highlights importance examining diverse sub-phenotypic ASD, features, comorbid conditions clinical correlates comprise underlying disorder.