Association between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population.

New CAR Research Sheds Light on

 

Universal Screening for Autism in Toddlers

TitleAssociation between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population.
Publication TypeJournal Article
Year of Publication2010
AuthorsSt Pourcain, B, Wang, K, Glessner, JT, Golding, J, Steer, C, Ring, SM, Skuse, DH, Grant, SFA, Hakonarson, H, Smith, GD, Smith, GDavey
JournalAm J Psychiatry
Volume167
Issue11
Pagination1364-72
Date Published2010 Nov
ISSN1535-7228
KeywordsAlleles, Child, Child Development Disorders, Pervasive, Child, Preschool, Chromosomes, Human, Pair 5, Cohort Studies, Communication Disorders, Education, Special, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Intelligence, Learning Disorders, Longitudinal Studies, Male, Neurocognitive Disorders, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Social Behavior, Stereotyped Behavior, United Kingdom
Abstract

OBJECTIVE: Recent genome-wide analysis identified a genetic variant on 5p14.1 (rs4307059), which is associated with risk for autism spectrum disorder. This study investigated whether rs4307059 also operates as a quantitative trait locus underlying a broader autism phenotype in the general population, focusing specifically on the social communication aspect of the spectrum.METHOD: Study participants were 7,313 children from the Avon Longitudinal Study of Parents and Children. Single-trait and joint-trait genotype associations were investigated for 29 measures related to language and communication, verbal intelligence, social interaction, and behavioral adjustment, assessed between ages 3 and 12 years. Analyses were performed in one-sided or directed mode and adjusted for multiple testing, trait interrelatedness, and random genotype dropout.RESULTS: Single phenotype analyses showed that an increased load of rs4307059 risk allele is associated with stereotyped conversation and lower pragmatic communication skills, as measured by the Children's Communication Checklist (at a mean age of 9.7 years). In addition a trend toward a higher frequency of identification of special educational needs (at a mean age of 11.8 years) was observed. Variation at rs4307059 was also associated with the phenotypic profile of studied traits. This joint signal was fully explained neither by single-trait associations nor by overall behavioral adjustment problems but suggested a combined effect, which manifested through multiple sub-threshold social, communicative, and cognitive impairments.CONCLUSIONS: Our results suggest that common variation at 5p14.1 is associated with social communication spectrum phenotypes in the general population and support the role of rs4307059 as a quantitative trait locus for autism spectrum disorder.

DOI10.1176/appi.ajp.2010.09121789
Alternate JournalAm J Psychiatry
PubMed ID20634369
PubMed Central IDPMC3008767
Grant ListG0600705 / / Medical Research Council / United Kingdom
G0400085 / / Medical Research Council / United Kingdom
076467 / / Wellcome Trust / United Kingdom
076467/Z05/z / / Wellcome Trust / United Kingdom
74882 / / Medical Research Council / United Kingdom
G9815508(74882) / / Medical Research Council / United Kingdom
G9815508 / / Medical Research Council / United Kingdom
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