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

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 (N(cases)/N(controls) = 1,204/6,491). 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 to middle 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 = 9.3 × 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 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.