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

Measurement equivalence of the autism symptom phenotype in children and youth / Eric DUKU in Journal of Child Psychology and Psychiatry, 54-12 (December 2013)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 54-12 (December 2013) . - p.1346-1355 Titre : Measurement equivalence of the autism symptom phenotype in children and youth Type de document : Texte imprimé et/ou numérique Auteurs : Eric DUKU, Auteur ; Peter SZATMARI, Auteur ; Tracy VAILLANCOURT, Auteur ; Stelios GEORGIADES, Auteur ; Ann THOMPSON, Auteur ; Xiao-Qing LIU, Auteur ; Andrew D. PATERSON, Auteur ; Terry BENNETT, Auteur Article en page(s) : p.1346-1355 Langues : Anglais (eng) Mots-clés : Autism Diagnostic Interview-Revised  measurement equivalence  autism spectrum disorder  confirmatory factor analysis  structural equation modelling Index. décimale : PER Périodiques Résumé : Background The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key underlying assumption of studies using the ADI-R is that it measures the same phenotypic constructs across different populations (i.e. males/females, younger/older, verbal/nonverbal). The objectives of this study were to evaluate alternative measurement models for the autism symptom phenotype based on the ADI-R algorithm items and to examine the measurement equivalence of the most parsimonious and best fitting model across subgroups of interest. Methods Data came from the Autism Genome Project consortium and consisted of 3,628 children aged 4–18 years (84.2% boys and 75% verbal). Twenty-eight algorithm items applicable to both verbal and nonverbal participants were used in the analysis. Measurement equivalence of the autism phenotype was examined using categorical confirmatory factor analysis. Results A second-order model resembling the proposed DSM-5 two-factor structure of the phenotype showed good overall fit, but not for all the subgroups. The autism symptom phenotype was best indexed by the first-order, six-factor measurement model proposed by Liu et al. (2011). This model was well fitting and measurement equivalent across subgroups of participants (age, verbal ability and sex). Conclusions The autism symptom phenotype is adequately characterized by a six-factor measurement model; this model appears to be measurement equivalent across subgroups of children and youth with ASD that differ in age, sex and verbal ability. The two-factor model provides equally good fit for the sample as a whole, but comparison of these two dimensions between subgroups that might differ in terms of age, sex or verbal ability is challenged by lack of measurement equivalence. En ligne : http://dx.doi.org/10.1111/jcpp.12103 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=219 [article] Measurement equivalence of the autism symptom phenotype in children and youth [Texte imprimé et/ou numérique] / Eric DUKU, Auteur ; Peter SZATMARI, Auteur ; Tracy VAILLANCOURT, Auteur ; Stelios GEORGIADES, Auteur ; Ann THOMPSON, Auteur ; Xiao-Qing LIU, Auteur ; Andrew D. PATERSON, Auteur ; Terry BENNETT, Auteur . - p.1346-1355. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 54-12 (December 2013) . - p.1346-1355 Mots-clés : Autism Diagnostic Interview-Revised  measurement equivalence  autism spectrum disorder  confirmatory factor analysis  structural equation modelling Index. décimale : PER Périodiques Résumé : Background The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key underlying assumption of studies using the ADI-R is that it measures the same phenotypic constructs across different populations (i.e. males/females, younger/older, verbal/nonverbal). The objectives of this study were to evaluate alternative measurement models for the autism symptom phenotype based on the ADI-R algorithm items and to examine the measurement equivalence of the most parsimonious and best fitting model across subgroups of interest. Methods Data came from the Autism Genome Project consortium and consisted of 3,628 children aged 4–18 years (84.2% boys and 75% verbal). Twenty-eight algorithm items applicable to both verbal and nonverbal participants were used in the analysis. Measurement equivalence of the autism phenotype was examined using categorical confirmatory factor analysis. Results A second-order model resembling the proposed DSM-5 two-factor structure of the phenotype showed good overall fit, but not for all the subgroups. The autism symptom phenotype was best indexed by the first-order, six-factor measurement model proposed by Liu et al. (2011). This model was well fitting and measurement equivalent across subgroups of participants (age, verbal ability and sex). Conclusions The autism symptom phenotype is adequately characterized by a six-factor measurement model; this model appears to be measurement equivalent across subgroups of children and youth with ASD that differ in age, sex and verbal ability. The two-factor model provides equally good fit for the sample as a whole, but comparison of these two dimensions between subgroups that might differ in terms of age, sex or verbal ability is challenged by lack of measurement equivalence. En ligne : http://dx.doi.org/10.1111/jcpp.12103 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=219

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism / V. J. VIELAND in Journal of Neurodevelopmental Disorders, 3-2 (June 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.113-23 Titre : Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism Type de document : Texte imprimé et/ou numérique Auteurs : V. J. VIELAND, Auteur ; J. HALLMAYER, Auteur ; Y. HUANG, Auteur ; Alistair T. PAGNAMENTA, Auteur ; D. PINTO, Auteur ; H. KHAN, Auteur ; A. P. MONACO, Auteur ; Andrew D. PATERSON, Auteur ; Stephen SCHERER, Auteur ; J. S. SUTCLIFFE, Auteur ; P. SZATMARI, Auteur Article en page(s) : p.113-23 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well. En ligne : http://dx.doi.org/10.1007/s11689-011-9072-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism [Texte imprimé et/ou numérique] / V. J. VIELAND, Auteur ; J. HALLMAYER, Auteur ; Y. HUANG, Auteur ; Alistair T. PAGNAMENTA, Auteur ; D. PINTO, Auteur ; H. KHAN, Auteur ; A. P. MONACO, Auteur ; Andrew D. PATERSON, Auteur ; Stephen SCHERER, Auteur ; J. S. SUTCLIFFE, Auteur ; P. SZATMARI, Auteur . - p.113-23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.113-23 Index. décimale : PER Périodiques Résumé : The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well. En ligne : http://dx.doi.org/10.1007/s11689-011-9072-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

---

1 (1 - 4 / 4)