Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders / Nadine PARKER ; Laurie J. HANNIGAN ; Espen HAGEN ; Pravesh PAREKH ; Alexey SHADRIN ; Piotr JAHOLKOWSKI ; Evgeniia FREI ; Viktoria BIRKENÆS ; Guy HINDLEY ; Laura HEGEMANN ; Elizabeth C. CORFIELD ; Martin TESLI ; Alexandra HAVDAHL ; Ole A. ANDREASSEN in Journal of Child Psychology and Psychiatry, 66-3 (March 2025)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 66-3 (March 2025) . - p.350-365 Titre : Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders Type de document : Texte imprimé et/ou numérique Auteurs : Nadine PARKER, Auteur ; Laurie J. HANNIGAN, Auteur ; Espen HAGEN, Auteur ; Pravesh PAREKH, Auteur ; Alexey SHADRIN, Auteur ; Piotr JAHOLKOWSKI, Auteur ; Evgeniia FREI, Auteur ; Viktoria BIRKENÆS, Auteur ; Guy HINDLEY, Auteur ; Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Martin TESLI, Auteur ; Alexandra HAVDAHL, Auteur ; Ole A. ANDREASSEN, Auteur Article en page(s) : p.350-365 Langues : Anglais (eng) Mots-clés : Emotional problems  behavioral problems  polygenic risk (PRS)  mood disorder  anxiety disorder  development  MoBa  MBRN Index. décimale : PER Périodiques Résumé : Background Symptoms related to mood and anxiety disorders (emotional disorders) often present in childhood and adolescence. Some of the genetic liability for mental disorders, and emotional and behavioral difficulties seems to be shared. Yet, it is unclear how genetic liability for emotional disorders and related traits influence trajectories of childhood behavioral and emotional difficulties, and if specific developmental patterns are associated with higher genetic liability for these disorders. Methods This study uses data from a genotyped sample of children (n?=?54,839) from the Norwegian Mother, Father, and Child Cohort Study (MoBa). We use latent growth models (1.5?5?years) and latent profile analyses (1.5?8?years) to quantify childhood trajectories and profiles of emotional and behavioral difficulties and diagnoses. We examine associations between these trajectories and profiles with polygenic scores for bipolar disorder (PGSBD), anxiety (PGSANX), depression (PGSDEP), and neuroticism (PGSNEUR). Results Associations between PGSDEP, PGSANX, and PGSNEUR, and emotional and behavioral difficulties in childhood were more persistent than age-specific across early childhood (1.5?5?years). Higher PGSANX and PGSDEP were associated with steeper increases in behavioral difficulties across early childhood. Latent profile analyses identified five profiles with different associations with emotional disorder diagnosis. All PGS were associated with the probability of classification into profiles characterized by some form of difficulties (vs. a normative reference profile), but only PGSBD was uniquely associated with a single developmental profile. Conclusions Genetic risk for mood disorders and related traits contribute to both a higher baseline level of, and a more rapid increase in, emotional and behavioral difficulties across early and middle childhood, with some indications for disorder-specific profiles. Our findings may inform research on developmental pathways to emotional disorders and the improvement of initiatives for early identification and targeted intervention. En ligne : https://doi.org/10.1111/jcpp.14063 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=548 [article] Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders [Texte imprimé et/ou numérique] / Nadine PARKER, Auteur ; Laurie J. HANNIGAN, Auteur ; Espen HAGEN, Auteur ; Pravesh PAREKH, Auteur ; Alexey SHADRIN, Auteur ; Piotr JAHOLKOWSKI, Auteur ; Evgeniia FREI, Auteur ; Viktoria BIRKENÆS, Auteur ; Guy HINDLEY, Auteur ; Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Martin TESLI, Auteur ; Alexandra HAVDAHL, Auteur ; Ole A. ANDREASSEN, Auteur . - p.350-365. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 66-3 (March 2025) . - p.350-365 Mots-clés : Emotional problems  behavioral problems  polygenic risk (PRS)  mood disorder  anxiety disorder  development  MoBa  MBRN Index. décimale : PER Périodiques Résumé : Background Symptoms related to mood and anxiety disorders (emotional disorders) often present in childhood and adolescence. Some of the genetic liability for mental disorders, and emotional and behavioral difficulties seems to be shared. Yet, it is unclear how genetic liability for emotional disorders and related traits influence trajectories of childhood behavioral and emotional difficulties, and if specific developmental patterns are associated with higher genetic liability for these disorders. Methods This study uses data from a genotyped sample of children (n?=?54,839) from the Norwegian Mother, Father, and Child Cohort Study (MoBa). We use latent growth models (1.5?5?years) and latent profile analyses (1.5?8?years) to quantify childhood trajectories and profiles of emotional and behavioral difficulties and diagnoses. We examine associations between these trajectories and profiles with polygenic scores for bipolar disorder (PGSBD), anxiety (PGSANX), depression (PGSDEP), and neuroticism (PGSNEUR). Results Associations between PGSDEP, PGSANX, and PGSNEUR, and emotional and behavioral difficulties in childhood were more persistent than age-specific across early childhood (1.5?5?years). Higher PGSANX and PGSDEP were associated with steeper increases in behavioral difficulties across early childhood. Latent profile analyses identified five profiles with different associations with emotional disorder diagnosis. All PGS were associated with the probability of classification into profiles characterized by some form of difficulties (vs. a normative reference profile), but only PGSBD was uniquely associated with a single developmental profile. Conclusions Genetic risk for mood disorders and related traits contribute to both a higher baseline level of, and a more rapid increase in, emotional and behavioral difficulties across early and middle childhood, with some indications for disorder-specific profiles. Our findings may inform research on developmental pathways to emotional disorders and the improvement of initiatives for early identification and targeted intervention. En ligne : https://doi.org/10.1111/jcpp.14063 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=548

Direct and indirect genetic effects on early neurodevelopmental traits / Laura HEGEMANN in Journal of Child Psychology and Psychiatry, 66-7 (July 2025)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 66-7 (July 2025) . - p.1053-1064 Titre : Direct and indirect genetic effects on early neurodevelopmental traits Type de document : Texte imprimé et/ou numérique Auteurs : Laura HEGEMANN, Auteur ; Espen EILERTSEN, Auteur ; Johanne HAGEN PETTERSEN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Rosa CHEESMAN, Auteur ; Leonard FRACH, Auteur ; Ludvig DAAE BJØRNDAL, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Alexandra HAVDAHL, Auteur ; Laurie J. HANNIGAN, Auteur Article en page(s) : p.1053-1064 Langues : Anglais (eng) Mots-clés : Autism  ADHD  MoBa  indirect genetic effects  genetic nurture  neurodevelopmental traits Index. décimale : PER Périodiques Résumé : Background Neurodevelopmental conditions are highly heritable. Recent studies have shown that genomic heritability estimates can be confounded by genetic effects mediated via the environment (indirect genetic effects). However, the relative importance of direct versus indirect genetic effects on early variability in traits related to neurodevelopmental conditions is unknown. Methods The sample included up to 24,692 parent-offspring trios from the Norwegian MoBa cohort. We use Trio-GCTA to estimate latent direct and indirect genetic effects on mother-reported neurodevelopmental traits at age of 3?years (restricted and repetitive behaviors and interests, inattention, hyperactivity, language, social, and motor development). Further, we investigate to what extent direct and indirect effects are attributable to common genetic variants associated with autism, ADHD, developmental dyslexia, educational attainment, and cognitive ability using polygenic scores (PGS) in regression modeling. Results We find evidence for contributions of direct and indirect latent common genetic effects to inattention (direct: explaining 4.8% of variance, indirect: 6.7%) hyperactivity (direct: 1.3%, indirect: 9.6%), and restricted and repetitive behaviors (direct: 0.8%, indirect: 7.3%). Direct effects best explained variation in social and communication, language, and motor development (5.1%?5.7%). Direct genetic effects on inattention were captured by PGS for ADHD, educational attainment, and cognitive ability, whereas direct genetic effects on language development were captured by cognitive ability, educational attainment, and autism PGS. Indirect genetic effects on neurodevelopmental traits were primarily captured by educational attainment and/or cognitive ability PGS. Conclusions Results were consistent with differential contributions to neurodevelopmental traits in early childhood from direct and indirect genetic effects. Indirect effects were particularly important for hyperactivity and restricted and repetitive behaviors and interests and may be linked to genetic variation associated with cognition and educational attainment. Our findings illustrate the importance of within-family methods for disentangling genetic processes that influence early neurodevelopmental traits, even when identifiable associations are small. En ligne : https://doi.org/10.1111/jcpp.14122 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=562 [article] Direct and indirect genetic effects on early neurodevelopmental traits [Texte imprimé et/ou numérique] / Laura HEGEMANN, Auteur ; Espen EILERTSEN, Auteur ; Johanne HAGEN PETTERSEN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Rosa CHEESMAN, Auteur ; Leonard FRACH, Auteur ; Ludvig DAAE BJØRNDAL, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Alexandra HAVDAHL, Auteur ; Laurie J. HANNIGAN, Auteur . - p.1053-1064. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 66-7 (July 2025) . - p.1053-1064 Mots-clés : Autism  ADHD  MoBa  indirect genetic effects  genetic nurture  neurodevelopmental traits Index. décimale : PER Périodiques Résumé : Background Neurodevelopmental conditions are highly heritable. Recent studies have shown that genomic heritability estimates can be confounded by genetic effects mediated via the environment (indirect genetic effects). However, the relative importance of direct versus indirect genetic effects on early variability in traits related to neurodevelopmental conditions is unknown. Methods The sample included up to 24,692 parent-offspring trios from the Norwegian MoBa cohort. We use Trio-GCTA to estimate latent direct and indirect genetic effects on mother-reported neurodevelopmental traits at age of 3?years (restricted and repetitive behaviors and interests, inattention, hyperactivity, language, social, and motor development). Further, we investigate to what extent direct and indirect effects are attributable to common genetic variants associated with autism, ADHD, developmental dyslexia, educational attainment, and cognitive ability using polygenic scores (PGS) in regression modeling. Results We find evidence for contributions of direct and indirect latent common genetic effects to inattention (direct: explaining 4.8% of variance, indirect: 6.7%) hyperactivity (direct: 1.3%, indirect: 9.6%), and restricted and repetitive behaviors (direct: 0.8%, indirect: 7.3%). Direct effects best explained variation in social and communication, language, and motor development (5.1%?5.7%). Direct genetic effects on inattention were captured by PGS for ADHD, educational attainment, and cognitive ability, whereas direct genetic effects on language development were captured by cognitive ability, educational attainment, and autism PGS. Indirect genetic effects on neurodevelopmental traits were primarily captured by educational attainment and/or cognitive ability PGS. Conclusions Results were consistent with differential contributions to neurodevelopmental traits in early childhood from direct and indirect genetic effects. Indirect effects were particularly important for hyperactivity and restricted and repetitive behaviors and interests and may be linked to genetic variation associated with cognition and educational attainment. Our findings illustrate the importance of within-family methods for disentangling genetic processes that influence early neurodevelopmental traits, even when identifiable associations are small. En ligne : https://doi.org/10.1111/jcpp.14122 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=562

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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