Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder / Zoe SCHMILOVICH in Research in Autism Spectrum Disorders, 99 (November)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 99 (November) . - 102055 Titre : Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder Type de document : texte imprimé Auteurs : Zoe SCHMILOVICH, Auteur ; Guillaume HUGUET, Auteur ; Qin HE, Auteur ; Amélie MUSA-JOHNSON, Auteur ; Elise DOUARD, Auteur ; Mor Absa LOUM, Auteur ; Calwing LIAO, Auteur ; Jay P. ROSS, Auteur ; Alexandre DIONNE-LAPORTE, Auteur ; Dan SPIEGELMAN, Auteur ; Martineau JEAN-LOUIS, Auteur ; Zohra SACI, Auteur ; Caroline HAYWARD, Auteur ; Tobias BANASCHEWSKI, Auteur ; Arun L.W. BOKDE, Auteur ; Sylvane DESRIVIERES, Auteur ; Herve LEMAITRE, Auteur ; Gunter SCHUMANN, Auteur ; Lan XIONG, Auteur ; Patrick A. DION, Auteur ; Sébastien JACQUEMONT, Auteur ; Boris CHAUMETTE, Auteur ; Guy A. ROULEAU, Auteur Article en page(s) : 102055 Langues : Anglais (eng) Mots-clés : CNTN5  CNV  intronic deletions  neurodevelopment  inherited Index. décimale : PER Périodiques Résumé : Background Contactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses. Method A CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database. Results Most (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs. Conclusions Intronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD. En ligne : https://doi.org/10.1016/j.rasd.2022.102055 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490 [article] Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder [texte imprimé] / Zoe SCHMILOVICH, Auteur ; Guillaume HUGUET, Auteur ; Qin HE, Auteur ; Amélie MUSA-JOHNSON, Auteur ; Elise DOUARD, Auteur ; Mor Absa LOUM, Auteur ; Calwing LIAO, Auteur ; Jay P. ROSS, Auteur ; Alexandre DIONNE-LAPORTE, Auteur ; Dan SPIEGELMAN, Auteur ; Martineau JEAN-LOUIS, Auteur ; Zohra SACI, Auteur ; Caroline HAYWARD, Auteur ; Tobias BANASCHEWSKI, Auteur ; Arun L.W. BOKDE, Auteur ; Sylvane DESRIVIERES, Auteur ; Herve LEMAITRE, Auteur ; Gunter SCHUMANN, Auteur ; Lan XIONG, Auteur ; Patrick A. DION, Auteur ; Sébastien JACQUEMONT, Auteur ; Boris CHAUMETTE, Auteur ; Guy A. ROULEAU, Auteur . - 102055. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 99 (November) . - 102055 Mots-clés : CNTN5  CNV  intronic deletions  neurodevelopment  inherited Index. décimale : PER Périodiques Résumé : Background Contactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses. Method A CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database. Results Most (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs. Conclusions Intronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD. En ligne : https://doi.org/10.1016/j.rasd.2022.102055 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490

A New Genetic Mechanism for Autism / Julie GAUTHIER  

Public ISBD in Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment / Stephen I. DEUTSCH   Titre : A New Genetic Mechanism for Autism Type de document : texte imprimé Auteurs : Julie GAUTHIER, Auteur ; Guy A. ROULEAU, Auteur Année de publication : 2011 Importance : p.104-124 Langues : Anglais (eng) Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques En ligne : http://dx.doi.org/10.5772/20864 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=143 in Autism Spectrum Disorders: The Role of Genetics in Diagnosis and Treatment / Stephen I. DEUTSCH   A New Genetic Mechanism for Autism [texte imprimé] / Julie GAUTHIER, Auteur ; Guy A. ROULEAU, Auteur . - 2011 . - p.104-124. Langues : Anglais (eng) Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques En ligne : http://dx.doi.org/10.5772/20864 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=143

Exemplaires(0)

Disponibilité
aucun exemplaire

Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood / Geneviève MORNEAU-VAILLANCOURT in Journal of Child Psychology and Psychiatry, 62-11 (November 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1320-1329 Titre : Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood Type de document : texte imprimé Auteurs : Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F.M. ANDLAUER, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Stéphane PAQUIN, Auteur ; Mara BRENDGEN, Auteur ; Frank VITARO, Auteur ; Jean-Philippe GOUIN, Auteur ; Jean R. SEGUIN, Auteur ; Éloi GAGNON, Auteur ; Rosa CHEESMAN, Auteur ; Nadine FORGET-DUBOIS, Auteur ; Guy A. ROULEAU, Auteur ; Gustavo TURECKI, Auteur ; Richard E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; Ginette DIONNE, Auteur ; Michel BOIVIN, Auteur Article en page(s) : p.1320-1329 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder  Child  Humans  Infant, Newborn  Loneliness  Longitudinal Studies  Multifactorial Inheritance/genetics  Prospective Studies  Social withdrawal  polygenic scores  preference for solitude  social wariness  trajectories Index. décimale : PER Périodiques Résumé : BACKGROUND: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. METHODS: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. RESULTS: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. CONCLUSIONS: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude. En ligne : http://dx.doi.org/10.1111/jcpp.13459 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood [texte imprimé] / Geneviève MORNEAU-VAILLANCOURT, Auteur ; Till F.M. ANDLAUER, Auteur ; Isabelle OUELLET-MORIN, Auteur ; Stéphane PAQUIN, Auteur ; Mara BRENDGEN, Auteur ; Frank VITARO, Auteur ; Jean-Philippe GOUIN, Auteur ; Jean R. SEGUIN, Auteur ; Éloi GAGNON, Auteur ; Rosa CHEESMAN, Auteur ; Nadine FORGET-DUBOIS, Auteur ; Guy A. ROULEAU, Auteur ; Gustavo TURECKI, Auteur ; Richard E. TREMBLAY, Auteur ; Sylvana M. CÔTÉ, Auteur ; Ginette DIONNE, Auteur ; Michel BOIVIN, Auteur . - p.1320-1329. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1320-1329 Mots-clés : Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder  Child  Humans  Infant, Newborn  Loneliness  Longitudinal Studies  Multifactorial Inheritance/genetics  Prospective Studies  Social withdrawal  polygenic scores  preference for solitude  social wariness  trajectories Index. décimale : PER Périodiques Résumé : BACKGROUND: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. METHODS: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. RESULTS: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. CONCLUSIONS: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude. En ligne : http://dx.doi.org/10.1111/jcpp.13459 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

The Mutational Spectrum of Neurodevelopmental Disorders / Nancy D. MERNER

Public ISBD in The Genetics of Neurodevelopmental Disorders / Kevin J. MITCHELL Titre : The Mutational Spectrum of Neurodevelopmental Disorders Type de document : texte imprimé Auteurs : Nancy D. MERNER, Auteur ; Patrick A. DION, Auteur ; Guy A. ROULEAU, Auteur Année de publication : 2015 Importance : p.49-68 Langues : Anglais (eng) Index. décimale : SCI-B SCI-B - Génétique Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=399 in The Genetics of Neurodevelopmental Disorders / Kevin J. MITCHELL The Mutational Spectrum of Neurodevelopmental Disorders [texte imprimé] / Nancy D. MERNER, Auteur ; Patrick A. DION, Auteur ; Guy A. ROULEAU, Auteur . - 2015 . - p.49-68. Langues : Anglais (eng) Index. décimale : SCI-B SCI-B - Génétique Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=399

Exemplaires(0)

Disponibilité
aucun exemplaire

The ongoing dissection of the genetic architecture of Autistic Spectrum Disorder / Rob F. GILLIS in Molecular Autism, (July 2011)  

Public ISBD [article]  inMolecular Autism > (July 2011) . - 29 p. Titre : The ongoing dissection of the genetic architecture of Autistic Spectrum Disorder Type de document : texte imprimé Auteurs : Rob F. GILLIS, Auteur ; Guy A. ROULEAU, Auteur Année de publication : 2011 Article en page(s) : 29 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The development of robust, non-hypothesis based case/control studies has led to a large push forward towards identifying common genetic variants that contribute to complex traits. However, despite many attempts, the search for common disease-predisposing variants in childhood developmental disorders has largely failed. Recently, a role for rare causal variants and de novo mutations is emerging in the genetic architecture of some of these disorders, particularly those which incur a large degree of selection against the phenotype. Here we examine these data as well as use classic genetic epidemiological approaches to gain insights into the genetic architecture of ASD. Future studies using next generation sequencing should elucidate the precise role de novo mutations play in disorders traditionally thought to have resulted from polygenic or common disease, common variants inheritance. En ligne : http://dx.doi.org/10.1186/2040-2392-2-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141 [article] The ongoing dissection of the genetic architecture of Autistic Spectrum Disorder [texte imprimé] / Rob F. GILLIS, Auteur ; Guy A. ROULEAU, Auteur . - 2011 . - 29 p. Langues : Anglais (eng) in Molecular Autism > (July 2011) . - 29 p. Index. décimale : PER Périodiques Résumé : The development of robust, non-hypothesis based case/control studies has led to a large push forward towards identifying common genetic variants that contribute to complex traits. However, despite many attempts, the search for common disease-predisposing variants in childhood developmental disorders has largely failed. Recently, a role for rare causal variants and de novo mutations is emerging in the genetic architecture of some of these disorders, particularly those which incur a large degree of selection against the phenotype. Here we examine these data as well as use classic genetic epidemiological approaches to gain insights into the genetic architecture of ASD. Future studies using next generation sequencing should elucidate the precise role de novo mutations play in disorders traditionally thought to have resulted from polygenic or common disease, common variants inheritance. En ligne : http://dx.doi.org/10.1186/2040-2392-2-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141

---

1 (1 - 5 / 5) Par page : 25 50 100 200