[article]
| Titre : |
Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
Beate ST POURCAIN, Auteur ; David SKUSE, Auteur ; William MANDY, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; George DAVEY SMITH, Auteur |
| Langues : |
Anglais (eng) |
| Index. décimale : |
PER Périodiques |
| Résumé : |
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 17years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N[less than or equal to]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[less than or equal to]105) 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 17years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P=9.3x109; genome-wide empirical P=0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P=7.9x108; 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. |
| En ligne : |
http://dx.doi.org/10.1186/2040-2392-5-18 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 |
in Molecular Autism > (February 2014)
[article] Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence [Texte imprimé et/ou numérique] / Beate ST POURCAIN, Auteur ; David SKUSE, Auteur ; William MANDY, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; George DAVEY SMITH, Auteur. Langues : Anglais ( eng) in Molecular Autism > (February 2014)
| Index. décimale : |
PER Périodiques |
| Résumé : |
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 17years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N[less than or equal to]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[less than or equal to]105) 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 17years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P=9.3x109; genome-wide empirical P=0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P=7.9x108; 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. |
| En ligne : |
http://dx.doi.org/10.1186/2040-2392-5-18 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 |
|
Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence in Molecular Autism, (February 2014)
