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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Molecular Autism 1/2014

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

Molecular Autism > Ausgabe 1/2014
Beate St Pourcain, David H Skuse, William P Mandy, Kai Wang, Hakon Hakonarson, Nicholas J Timpson, David M Evans, John P Kemp, Susan M Ring, Wendy L McArdle, Jean Golding, George Davey Smith
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Electronic supplementary material

The online version of this article (doi:10.​1186/​2040-2392-5-18) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

BSP and KW carried out the statistical analysis. BSP, DME, JPK, SMR and WLM were involved in the preparation of the genotype information. BSP, DHS, WPM and GDS participated in the design of the study. BSP, DHS, WPM, KW, HH, NJT, DMW, JPK, JG and GDS helped to draft the manuscript. All authors read and approved the final manuscript.



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.


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 ≤ 10−5) were also followed up in Autism Genetic Resource Exchange pedigrees (N = 793) and the Autism Case Control cohort (Ncases/Ncontrols = 1,204/6,491).


GCTA heritability was strongest in childhood (h2(8 years) = 0.24) and especially in later adolescence (h2(17 years) = 0.45), with a marked drop during early to middle adolescence (h2(11 years) = 0.16 and h2(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 × 10−9; genome-wide empirical P = 0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P = 7.9 × 10−8; 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 Pco-location = 0.007).


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.
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