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

Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes / Jean-Baptiste PINGAULT in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1125-1139 Titre : Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Jean-Baptiste PINGAULT, Auteur ; Andrea G. ALLEGRINI, Auteur ; Tracy ODIGIE, Auteur ; Leonard FRACH, Auteur ; Jessie R. BALDWIN, Auteur ; Frühling V. RIJSDIJK, Auteur ; Frank DUDBRIDGE, Auteur Année de publication : 2022 Article en page(s) : p.1125-1139 Langues : Anglais (eng) Mots-clés : Cohort Studies  Environmental Exposure/adverse effects  Genetic Predisposition to Disease  Genome-Wide Association Study  Humans  Midazolam  Multifactorial Inheritance  Phenotype  Polygenic scores  biases  environment  epidemiology  phenotypes Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified as environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants and an outcome in a single value for each individual. Ever lowering costs have enabled the genotyping of many samples relevant to child psychology and psychiatry research, including cohort studies, leading to the proliferation of polygenic score studies. It is tempting to assume that associations detected between polygenic scores and phenotypes in those studies only reflect genetic effects. However, such associations can reflect many pathways (e.g. via environmental mediation) and biases. METHODS: Here, we provide a comprehensive overview of the many reasons why associations between polygenic scores, environmental exposures, and phenotypes exist. We include formal representations of common analyses in polygenic score studies using structural equation modelling. We derive biases, provide illustrative empirical examples and, when possible, mention steps that can be taken to alleviate those biases. RESULTS: Structural equation models and derivations show the many complexities arising from jointly modelling polygenic scores with environmental exposures and phenotypes. Counter-intuitive examples include that: (a) associations between polygenic scores and phenotypes may exist even in the absence of direct genetic effects; (b) associations between child polygenic scores and environmental exposures can exist in the absence of evocative/active gene-environment correlations; and (c) adjusting an exposure-outcome association for a polygenic score can increase rather than decrease bias. CONCLUSIONS: Strikingly, using polygenic scores may, in some cases, lead to more bias than not using them. Appropriately conducting and interpreting polygenic score studies thus requires researchers in child psychology and psychiatry and beyond to be versed in both epidemiological and genetic methods or build on interdisciplinary collaborations. En ligne : http://dx.doi.org/10.1111/jcpp.13607 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 [article] Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes [Texte imprimé et/ou numérique] / Jean-Baptiste PINGAULT, Auteur ; Andrea G. ALLEGRINI, Auteur ; Tracy ODIGIE, Auteur ; Leonard FRACH, Auteur ; Jessie R. BALDWIN, Auteur ; Frühling V. RIJSDIJK, Auteur ; Frank DUDBRIDGE, Auteur . - 2022 . - p.1125-1139. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1125-1139 Mots-clés : Cohort Studies  Environmental Exposure/adverse effects  Genetic Predisposition to Disease  Genome-Wide Association Study  Humans  Midazolam  Multifactorial Inheritance  Phenotype  Polygenic scores  biases  environment  epidemiology  phenotypes Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified as environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants and an outcome in a single value for each individual. Ever lowering costs have enabled the genotyping of many samples relevant to child psychology and psychiatry research, including cohort studies, leading to the proliferation of polygenic score studies. It is tempting to assume that associations detected between polygenic scores and phenotypes in those studies only reflect genetic effects. However, such associations can reflect many pathways (e.g. via environmental mediation) and biases. METHODS: Here, we provide a comprehensive overview of the many reasons why associations between polygenic scores, environmental exposures, and phenotypes exist. We include formal representations of common analyses in polygenic score studies using structural equation modelling. We derive biases, provide illustrative empirical examples and, when possible, mention steps that can be taken to alleviate those biases. RESULTS: Structural equation models and derivations show the many complexities arising from jointly modelling polygenic scores with environmental exposures and phenotypes. Counter-intuitive examples include that: (a) associations between polygenic scores and phenotypes may exist even in the absence of direct genetic effects; (b) associations between child polygenic scores and environmental exposures can exist in the absence of evocative/active gene-environment correlations; and (c) adjusting an exposure-outcome association for a polygenic score can increase rather than decrease bias. CONCLUSIONS: Strikingly, using polygenic scores may, in some cases, lead to more bias than not using them. Appropriately conducting and interpreting polygenic score studies thus requires researchers in child psychology and psychiatry and beyond to be versed in both epidemiological and genetic methods or build on interdisciplinary collaborations. En ligne : http://dx.doi.org/10.1111/jcpp.13607 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486

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