2 recherche sur le mot-clé 'Genome-wide linkage'

Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families / M. WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.5 Titre : Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; Deborah A. BILDER, Auteur ; J. MORGAN, Auteur ; L. JEROMINSKI, Auteur ; T. DARLINGTON, Auteur ; T. DYER, Auteur ; Andrew D. PATERSON, Auteur ; H. COON, Auteur Article en page(s) : p.5 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Genetic association  Genome-wide linkage  Head circumference (HC) Index. décimale : PER Périodiques Résumé : BACKGROUND: It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. METHODS: HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. RESULTS: We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). CONCLUSIONS: Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9187-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; Deborah A. BILDER, Auteur ; J. MORGAN, Auteur ; L. JEROMINSKI, Auteur ; T. DARLINGTON, Auteur ; T. DYER, Auteur ; Andrew D. PATERSON, Auteur ; H. COON, Auteur . - p.5. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.5 Mots-clés : Autism spectrum disorder (ASD)  Genetic association  Genome-wide linkage  Head circumference (HC) Index. décimale : PER Périodiques Résumé : BACKGROUND: It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. METHODS: HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. RESULTS: We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). CONCLUSIONS: Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9187-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees / M. WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Titre : A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. SZATMARI, Auteur Année de publication : 2018 Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. SZATMARI, Auteur . - 2018 . - 20 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386