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

St Pourcain, B., Skuse, D. H., Mandy, W. P., Wang, K., Hakonarson, H., Timpson, N. J., et al. (2014). Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence. Molecular Autism, 5: 18. doi:10.1186/2040-2392-5-18.

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© 2014 St Pourcain et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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St Pourcain, Beate1, Author           
Skuse, David H, Author
Mandy, William P, Author
Wang, Kai, Author
Hakonarson, Hakon, Author
Timpson, Nicholas J, Author
Evans, David M, Author
Kemp, John P, Author
Ring, Susan M, Author
McArdle, Wendy L, Author
Golding, Jean, Author
Smith, George Davey, Author
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1University of Bristol, Bristol, UK, ou_persistent22              

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 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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Language(s): eng - English
 Dates: 2014
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1186/2040-2392-5-18
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Title: Molecular Autism
Source Genre: Journal
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Pages: - Volume / Issue: 5 Sequence Number: 18 Start / End Page: - Identifier: ISSN: 2040-2392