Genome-wide analyses of vocabulary size in infancy and toddlerhood: Associations with attention-deficit/hyperactivity disorder, literacy, and cognition-related traits

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• dc.contributor.author Verhoef, Ellen
• dc.contributor.author EAGLE Working Group
• dc.contributor.author St. Pourcain, Beate
• dc.contributor.author St. Pourcain, Beate
• dc.date.accessioned 2024-07-05T06:56:10Z
• dc.date.available 2024-07-05T06:56:10Z
• dc.date.issued 2024
• dc.description.abstract Background: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). Methods: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. Results: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = -0.74), highlighting developmental heterogeneity. Conclusions: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
• dc.description.abstract Background: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). Methods: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. Results: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = -0.74), highlighting developmental heterogeneity. Conclusions: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
• dc.description.sponsorship EV, EE, FS, SEF, and BSP were funded by the Max Planck Society. TSA was supported by the Novo Nordisk Foundation (Grant No. NNF18OC0052457). ATM is supported by the National Health and Medical Research Council. CS was supported by an Australian Government National Health and Medical Research Council Postgraduate Research Scholarship. EH receives funding from the National Health and Medical Research Council Australia, Australian Research Council, Medical Research Future Fund, and Tour de Cure. MB is funded by an NWO VICI grant (Grant No. VI.C.211.054) and an ERC consolidation grant (WELL-BEING 771057). MG is funded by a Miguel Servet II fellowship (CPII18/00018) awarded by the Spanish Institute of Health Carlos III. We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033 and support from the Generalitat de Catalunya through the CERCA (Centres de Recerca de Catalunya) Program. SH receives support from the UK National Institute for Health Research through the academic clinical fellowship scheme. KR is supported by a Sir Henry Wellcome Postdoctoral Fellowship. CYS and JLM are supported by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00032/02). OAA is supported by KG Jebsen Stiftelsen, Research Council of Norway (Grant No. 223273, 273291, 324252). EY receives support from Research Council of Norway (Grant Nos. 262177 and 288083). PRN was supported by grants from the European Research Council (AdG SELECTionPREDISPOSED #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”), Novo Nordisk Foundation Grant No. 54741, and the Norwegian Diabetes Association. CAMC receives support from the European Union’s Horizon 2020 Research and Innovation Programme (Grant agreement No. 848158) (EarlyCause Project). BSP, EV, and the EAGLE Working Group report that the EAGLE Working Group is one of the named authors and that all members qualify for authorship.
• dc.format.mimetype application/pdf
• dc.identifier.citation Verhoef E, Allegrini AG, Jansen PR, Lange K, Wang CA, Morgan AT, et al. Genome-wide analyses of vocabulary size in infancy and toddlerhood: Associations with attention-deficit/hyperactivity disorder, literacy, and cognition-related traits. Biol Psychiatry. 2024 May 1;95(9):859-69. DOI: 10.1016/j.biopsych.2023.11.025
• dc.identifier.doi http://dx.doi.org/10.1016/j.biopsych.2023.11.025
• dc.identifier.issn 0006-3223
• dc.identifier.uri http://hdl.handle.net/10230/60667
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Biol Psychiatry. 2024 May 1;95(9):859-69
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848158
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
• dc.rights © 2023 Society of Biological Psychiatry. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ADHD
• dc.subject.keyword Cognition
• dc.subject.keyword Development
• dc.subject.keyword GWAS
• dc.subject.keyword SEM
• dc.subject.keyword Vocabulary
• dc.title Genome-wide analyses of vocabulary size in infancy and toddlerhood: Associations with attention-deficit/hyperactivity disorder, literacy, and cognition-related traits
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion