Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence

St Pourcain, Beate, Skuse, David H., Mandy, William P., Wang, Kai, Hakonarson, Hakon, Timpson, Nicholas J., Evans, David M., Kemp, John P., Ring, Susan M., McArdle, Wendy L., Golding, Jean and Smith, George Davey (2014) Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence. Molecular Autism, 5 1: . doi:10.1186/2040-2392-5-18

Author St Pourcain, Beate
Skuse, David H.
Mandy, William P.
Wang, Kai
Hakonarson, Hakon
Timpson, Nicholas J.
Evans, David M.
Kemp, John P.
Ring, Susan M.
McArdle, Wendy L.
Golding, Jean
Smith, George Davey
Title Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence
Journal name Molecular Autism   Check publisher's open access policy
ISSN 2040-2392
Publication date 2014-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1186/2040-2392-5-18
Open Access Status DOI
Volume 5
Issue 1
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Language eng
Subject 1312 Molecular Biology
2806 Developmental Neuroscience
1309 Developmental Biology
2738 Psychiatry and Mental health
Abstract Background: Social-communication abilities are heritable traits, and their impairments overlap with the autism continuum. To characterise the genetic architecture of social-communication difficulties developmentally and identify genetic links with the autistic dimension, we conducted a genome-wide screen of social-communication problems at multiple time-points during childhood and adolescence. Methods. Social-communication difficulties were ascertained at ages 8, 11, 14 and 17 years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N ≤ 5,628) using mother-reported Social Communication Disorder Checklist scores. Genome-wide Complex Trait Analysis (GCTA) was conducted for all phenotypes. The time-points with the highest GCTA heritability were subsequently analysed for single SNP association genome-wide. Type I error in the presence of measurement relatedness and the likelihood of observing SNP signals near known autism susceptibility loci (co-location) were assessed via large-scale, genome-wide permutations. Association signals (P ≤ 10 were also followed up in Autism Genetic Resource Exchange pedigrees (N = 793) and the Autism Case Control cohort (N N = 1,204/6,491). Results: GCTA heritability was strongest in childhood (h (8 years) = 0.24) and especially in later adolescence (h (17 years) = 0.45), with a marked drop during early to middle adolescence (h (11 years) = 0.16 and h(14 years) = 0.08). Genome-wide screens at ages 8 and 17 years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P = 9.3 × 10 genome-wide empirical P = 0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P = 7.9 × 10 genome-wide empirical P = 0.085). None of these signals contributed to risk for autism. However, the co-location of population-based signals and autism susceptibility loci harbouring rare mutations, such as PLCB1, is unlikely to be due to chance (genome-wide empirical P co-location = 0.007). Conclusions: Our findings suggest that measurable common genetic effects for social-communication difficulties vary developmentally and that these changes may affect detectable overlaps with the autism spectrum.
Keyword Alspac
Genome wide association
Copy number variation
Autistic Traits
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 092731
MRC G0800582
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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