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Publication Detail
Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    St Pourcain B, Skuse DH, Mandy WP, Wang K, Hakonarson H, Timpson NJ, Evans DM, Kemp JP, Ring SM, McArdle WL, Golding J, Smith GD
  • Publication date:
    24/02/2014
  • Pagination:
    18, ?
  • Journal:
    Mol Autism
  • Volume:
    5
  • Issue:
    1
  • Status:
    Published online
  • Country:
    England
  • Print ISSN:
    2040-2392
  • PII:
    2040-2392-5-18
  • Language:
    eng
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 ≤ 10-5) were also followed up in Autism Genetic Resource Exchange pedigrees (N = 793) and the Autism Case Control cohort (Ncases/Ncontrols = 1,204/6,491). RESULTS: 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). 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.
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Clinical, Edu & Hlth Psychology
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