Common variation contributes to the genetic architecture of social communication traits / Beate ST POURCAIN in Molecular Autism, (September 2013)  

Public ISBD [article]  inMolecular Autism > (September 2013) Titre : Common variation contributes to the genetic architecture of social communication traits Type de document : Texte imprimé et/ou numérique Auteurs : Beate ST POURCAIN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Wei ANG, Auteur ; Nicole WARRINGTON, Auteur ; Joseph GLESSNER, Auteur ; Kai WANG, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; Hakon HAKONARSON, Auteur ; Craig E. PENNELL, Auteur ; George SMITH, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development. However, little is known about the underlying genetic architecture of this phenotype. We performed a genome-wide association study on parent-reported social communication problems using items of the children's communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a sample of children with comparable measures from Western Australia (RAINE, N = 1364). Two of our seven independent top signals (P-discovery 1.0E-05) were replicated (0.009 P-replication [less than or equal to]0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta-P = 2.5E-07) and 14q22.1 (rs2352908, meta-P = 1.1E-06). The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region. The strongest candidate locus within this genomic area was TRIM27. This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism. The signal at 14q22.1 was found within a gene-poor region.Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome (h2(SE) = 0.18(0.066), P = 0.0027). Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Common variation contributes to the genetic architecture of social communication traits [Texte imprimé et/ou numérique] / Beate ST POURCAIN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Wei ANG, Auteur ; Nicole WARRINGTON, Auteur ; Joseph GLESSNER, Auteur ; Kai WANG, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; Hakon HAKONARSON, Auteur ; Craig E. PENNELL, Auteur ; George SMITH, Auteur. Langues : Anglais (eng) in Molecular Autism > (September 2013) Index. décimale : PER Périodiques Résumé : Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development. However, little is known about the underlying genetic architecture of this phenotype. We performed a genome-wide association study on parent-reported social communication problems using items of the children's communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a sample of children with comparable measures from Western Australia (RAINE, N = 1364). Two of our seven independent top signals (P-discovery 1.0E-05) were replicated (0.009 P-replication [less than or equal to]0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta-P = 2.5E-07) and 14q22.1 (rs2352908, meta-P = 1.1E-06). The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region. The strongest candidate locus within this genomic area was TRIM27. This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism. The signal at 14q22.1 was found within a gene-poor region.Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome (h2(SE) = 0.18(0.066), P = 0.0027). Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Interventions used with an Australian sample of preschool children with autism spectrum disorders / Mark CARTER in Research in Autism Spectrum Disorders, 5-3 (July-September 2011)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 5-3 (July-September 2011) . - p.1033-1041 Titre : Interventions used with an Australian sample of preschool children with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Mark CARTER, Auteur ; Jacqueline ROBERTS, Auteur ; Katrina WILLIAMS, Auteur ; David EVANS, Auteur ; Trevor R. PARMENTER, Auteur ; Natalie SILOVE, Auteur ; Trevor CLARK, Auteur ; Anthony WARREN, Auteur Année de publication : 2011 Article en page(s) : p.1033-1041 Langues : Anglais (eng) Mots-clés : Autism  Parents  Survey  Treatment  Education  Complementary and alternative medicine Index. décimale : PER Périodiques Résumé : This study examined the previous and current range of educational, therapy, medical and CAM interventions used by a clearly described Australian sample of 84 families of preschool-aged children with autism spectrum disorders who were enrolled in a controlled trial of early intervention services. With regard to educational and therapy interventions, the most frequently used services were speech–language pathology, preschool and childcare, generic early intervention, and occupational therapy. With the exception of preschool and childcare, the access frequency for most of these services indicated they were used at relatively low intensity. Exclusion diets, oils/fatty acids and vitamin and mineral supplements were the primary CAM interventions used by families. There was no clear evidence of a relationship between the number of interventions used by families and developmental status although this may have been due to the relatively recent diagnoses. Implications of these findings and directions for future research are discussed. En ligne : http://dx.doi.org/10.1016/j.rasd.2010.11.009 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=119 [article] Interventions used with an Australian sample of preschool children with autism spectrum disorders [Texte imprimé et/ou numérique] / Mark CARTER, Auteur ; Jacqueline ROBERTS, Auteur ; Katrina WILLIAMS, Auteur ; David EVANS, Auteur ; Trevor R. PARMENTER, Auteur ; Natalie SILOVE, Auteur ; Trevor CLARK, Auteur ; Anthony WARREN, Auteur . - 2011 . - p.1033-1041. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 5-3 (July-September 2011) . - p.1033-1041 Mots-clés : Autism  Parents  Survey  Treatment  Education  Complementary and alternative medicine Index. décimale : PER Périodiques Résumé : This study examined the previous and current range of educational, therapy, medical and CAM interventions used by a clearly described Australian sample of 84 families of preschool-aged children with autism spectrum disorders who were enrolled in a controlled trial of early intervention services. With regard to educational and therapy interventions, the most frequently used services were speech–language pathology, preschool and childcare, generic early intervention, and occupational therapy. With the exception of preschool and childcare, the access frequency for most of these services indicated they were used at relatively low intensity. Exclusion diets, oils/fatty acids and vitamin and mineral supplements were the primary CAM interventions used by families. There was no clear evidence of a relationship between the number of interventions used by families and developmental status although this may have been due to the relatively recent diagnoses. Implications of these findings and directions for future research are discussed. En ligne : http://dx.doi.org/10.1016/j.rasd.2010.11.009 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=119

A randomised controlled trial of two early intervention programs for young children with autism: Centre-based with parent program and home-based / Jacqueline ROBERTS in Research in Autism Spectrum Disorders, 5-4 (October-December 2011)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 5-4 (October-December 2011) . - p.1553-1566 Titre : A randomised controlled trial of two early intervention programs for young children with autism: Centre-based with parent program and home-based Type de document : Texte imprimé et/ou numérique Auteurs : Jacqueline ROBERTS, Auteur ; Katrina WILLIAMS, Auteur ; Mark CARTER, Auteur ; David EVANS, Auteur ; Trevor R. PARMENTER, Auteur ; Natalie SILOVE, Auteur ; Trevor CLARK, Auteur ; Anthony WARREN, Auteur Année de publication : 2011 Article en page(s) : p.1553-1566 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Early-intervention  Home-based  Centre-based  Parent programs Index. décimale : PER Périodiques Résumé : This study compares outcomes of early intervention programs for young children with autism; an individualised home-based program (HB), a small group centre-based program for children combined with a parent training and support group (CB) and a non-treatment comparison group (WL). Outcome measures of interest include social and communication skill development in children, quality of life and stress for parents. Eligible (diagnosed ASD, preschool age) participants were randomised into 2 groups HB (n = 28) and CB (n = 28). A WL (n = 29) comparison group was also recruited. HB and CB groups had 12-month programs. Pre and post assessments were conducted using formal and informal measures. Children in the CB group improved significantly more than HB and WL groups on some social and communication measures. On parent measures outcomes varied with CB group parents making the most gains in perception of competence and quality of life. The small group centre-based program combined with parent program resulted in the best most cost effective outcomes for children and families however this is not an option for all. The CB program did not suit some children and families. The heterogeneity of the autism population indicates that a range of intervention options is necessary to meet the needs of children with autism and their families. En ligne : http://dx.doi.org/10.1016/j.rasd.2011.03.001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=126 [article] A randomised controlled trial of two early intervention programs for young children with autism: Centre-based with parent program and home-based [Texte imprimé et/ou numérique] / Jacqueline ROBERTS, Auteur ; Katrina WILLIAMS, Auteur ; Mark CARTER, Auteur ; David EVANS, Auteur ; Trevor R. PARMENTER, Auteur ; Natalie SILOVE, Auteur ; Trevor CLARK, Auteur ; Anthony WARREN, Auteur . - 2011 . - p.1553-1566. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 5-4 (October-December 2011) . - p.1553-1566 Mots-clés : Autism spectrum disorders  Early-intervention  Home-based  Centre-based  Parent programs Index. décimale : PER Périodiques Résumé : This study compares outcomes of early intervention programs for young children with autism; an individualised home-based program (HB), a small group centre-based program for children combined with a parent training and support group (CB) and a non-treatment comparison group (WL). Outcome measures of interest include social and communication skill development in children, quality of life and stress for parents. Eligible (diagnosed ASD, preschool age) participants were randomised into 2 groups HB (n = 28) and CB (n = 28). A WL (n = 29) comparison group was also recruited. HB and CB groups had 12-month programs. Pre and post assessments were conducted using formal and informal measures. Children in the CB group improved significantly more than HB and WL groups on some social and communication measures. On parent measures outcomes varied with CB group parents making the most gains in perception of competence and quality of life. The small group centre-based program combined with parent program resulted in the best most cost effective outcomes for children and families however this is not an option for all. The CB program did not suit some children and families. The heterogeneity of the autism population indicates that a range of intervention options is necessary to meet the needs of children with autism and their families. En ligne : http://dx.doi.org/10.1016/j.rasd.2011.03.001 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=126

Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence / Beate ST POURCAIN in Molecular Autism, (February 2014)  

Public ISBD [article]  inMolecular Autism > (February 2014) 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 [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

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