|Title||Association between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||St Pourcain, B, Wang, K, Glessner, JT, Golding, J, Steer, C, Ring, SM, Skuse, DH, Grant, SFA, Hakonarson, H, Smith, GD, Smith, GDavey|
|Journal||Am J Psychiatry|
|Date Published||2010 Nov|
|Keywords||Alleles, 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 Disabilities, Longitudinal Studies, Male, Neurocognitive Disorders, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Social Behavior, Stereotyped Behavior, United Kingdom|
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.
|Alternate Journal||Am J Psychiatry|
|PubMed Central ID||PMC3008767|
|Grant List||G0600705 / / 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