Early manifestations of genetic risk for neurodevelopmental disorders / Ragna Bugge ASKELAND in Journal of Child Psychology and Psychiatry, 63-7 (July 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-7 (July 2022) . - p.810-819 Titre : Early manifestations of genetic risk for neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : Ragna Bugge ASKELAND, Auteur ; Laurie J. HANNIGAN, Auteur ; Helga ASK, Auteur ; Ziada AYORECH, Auteur ; Martin TESLI, Auteur ; Elizabeth CORFIELD, Auteur ; Per MAGNUS, Auteur ; Pål Rasmus NJØLSTAD, Auteur ; Ole A. ANDREASSEN, Auteur ; George DAVEY SMITH, Auteur ; Ted REICHBORN-KJENNERUD, Auteur ; Alexandra HAVDAHL, Auteur Article en page(s) : p.810-819 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with  Hyperactivity/complications/epidemiology/genetics  Autism Spectrum Disorder/complications/epidemiology/genetics  Child  Child, Preschool  Cohort Studies  Female  Humans  Male  Mothers  Neurodevelopmental Disorders/complications/epidemiology/genetics  Risk Factors  Adhd  MoBa  Polygenic risk score  autism  hyperactivity  inattention  language and motor difficulties  neurodevelopmental disorders  repetitive behavior  schizophrenia  social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls. METHODS: Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15?205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18?months, 3, 5 and 8?years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable. RESULTS: Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8?years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18?months, motor difficulties at 36?months, and hyperactivity and inattention at 8?years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18?months was, however, stronger in boys. CONCLUSIONS: Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits. En ligne : http://dx.doi.org/10.1111/jcpp.13528 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 [article] Early manifestations of genetic risk for neurodevelopmental disorders [Texte imprimé et/ou numérique] / Ragna Bugge ASKELAND, Auteur ; Laurie J. HANNIGAN, Auteur ; Helga ASK, Auteur ; Ziada AYORECH, Auteur ; Martin TESLI, Auteur ; Elizabeth CORFIELD, Auteur ; Per MAGNUS, Auteur ; Pål Rasmus NJØLSTAD, Auteur ; Ole A. ANDREASSEN, Auteur ; George DAVEY SMITH, Auteur ; Ted REICHBORN-KJENNERUD, Auteur ; Alexandra HAVDAHL, Auteur . - p.810-819. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-7 (July 2022) . - p.810-819 Mots-clés : Attention Deficit Disorder with  Hyperactivity/complications/epidemiology/genetics  Autism Spectrum Disorder/complications/epidemiology/genetics  Child  Child, Preschool  Cohort Studies  Female  Humans  Male  Mothers  Neurodevelopmental Disorders/complications/epidemiology/genetics  Risk Factors  Adhd  MoBa  Polygenic risk score  autism  hyperactivity  inattention  language and motor difficulties  neurodevelopmental disorders  repetitive behavior  schizophrenia  social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls. METHODS: Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15?205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18?months, 3, 5 and 8?years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable. RESULTS: Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8?years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18?months, motor difficulties at 36?months, and hyperactivity and inattention at 8?years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18?months was, however, stronger in boys. CONCLUSIONS: Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits. En ligne : http://dx.doi.org/10.1111/jcpp.13528 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477

Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study / Laura HEGEMANN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 25p. Titre : Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study Type de document : Texte imprimé et/ou numérique Auteurs : Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Adrian Dahl ASKELUND, Auteur ; Andrea G. ALLEGRINI, Auteur ; Ragna Bugge ASKELAND, Auteur ; Angelica RONALD, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Ole A. ANDREASSEN, Auteur ; Laurie J. HANNIGAN, Auteur ; Alexandra. HAVDAHL, Auteur Article en page(s) : 25p. Langues : Anglais (eng) Mots-clés : Humans  Norway  Female  Male  Phenotype  Child, Preschool  Cohort Studies  Neurodevelopmental Disorders/genetics/diagnosis  Mothers  Autistic Disorder/genetics  Genetic Predisposition to Disease  Adult  Fathers  Genome-Wide Association Study  Attention Deficit Disorder with Hyperactivity/genetics/diagnosis  Schizophrenia/genetics  Genetic Heterogeneity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r(g) range = -?0.27-0.78), ADHD (items r(g) range = -?0.40-1), and schizophrenia (items r(g) range = -?0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs. En ligne : https://dx.doi.org/10.1186/s13229-024-00599-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study [Texte imprimé et/ou numérique] / Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Adrian Dahl ASKELUND, Auteur ; Andrea G. ALLEGRINI, Auteur ; Ragna Bugge ASKELAND, Auteur ; Angelica RONALD, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Ole A. ANDREASSEN, Auteur ; Laurie J. HANNIGAN, Auteur ; Alexandra. HAVDAHL, Auteur . - 25p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 25p. Mots-clés : Humans  Norway  Female  Male  Phenotype  Child, Preschool  Cohort Studies  Neurodevelopmental Disorders/genetics/diagnosis  Mothers  Autistic Disorder/genetics  Genetic Predisposition to Disease  Adult  Fathers  Genome-Wide Association Study  Attention Deficit Disorder with Hyperactivity/genetics/diagnosis  Schizophrenia/genetics  Genetic Heterogeneity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r(g) range = -?0.27-0.78), ADHD (items r(g) range = -?0.40-1), and schizophrenia (items r(g) range = -?0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs. En ligne : https://dx.doi.org/10.1186/s13229-024-00599-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

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