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

ABSTRACT: 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.

SUBMITTER: St Pourcain B

PROVIDER: S-EPMC3940728 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

St Pourcain Beate B Skuse David H DH Mandy William P WP Wang Kai K Hakonarson Hakon H Timpson Nicholas J NJ Evans David M DM Kemp John P JP Ring Susan M SM McArdle Wendy L WL Golding Jean J Smith George Davey GD

Molecular autism 20140224 1

<h4>Background</h4>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.<h4>Methods</h4>Social-communication difficulties were ascertained at ages 8, 11, 14 and 17 years ...[more]

PMID: 24564958

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

Publications

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

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