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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)

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

Results: GCTA heritability was strongest in childhood (h(2)((8 years)) = 0.24) and especially in later adolescence (h(2) ((17 years)) = 0.45), with a marked drop during early tomiddle adolescence (h(2) ((11 years))= 0.16 and h(2)((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 = 9.3x10(-9); genome-wide empirical P = 0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P = 7.9x10(-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).

Conclusions: Our findings suggest that measurable common genetic effects for social-communication

Original languageEnglish
Article number18
Pages (from-to)18
Number of pages12
JournalMolecular Autism
Volume5
Issue number1
DOIs
Publication statusPublished - 24 Feb 2014

Keywords

  • ALSPAC
  • ASD
  • Autism
  • GCTA heritability
  • GWAS Social communication
  • GENOME-WIDE ASSOCIATION
  • COPY-NUMBER VARIATION
  • AUTISTIC TRAITS
  • GENERAL-POPULATION
  • COMPLEX TRAITS
  • DISORDERS
  • ETIOLOGY
  • LINKAGE
  • GENOTYPES
  • VARIANTS

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