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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Verhoef, Ellen
Allegrini, Andrea G
Jansen, Philip R
Lange, Katherine
Wang, Carol A
Morgan, Angela T
Ahluwalia, Tarunveer S
Symeonides, Christos
EAGLE Working Group
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2023
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http://creativecommons.org/licenses/by/4.0/
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.

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Biological Psychiatry
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© 2023 Society of Biological Psychiatry. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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Biological sciences
Biomedical and clinical sciences
Psychology
ADHD
Cognition
Development
GWAS
SEM
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Verhoef, E; Allegrini, AG; Jansen, PR; Lange, K; Wang, CA; Morgan, AT; Ahluwalia, TS; Symeonides, C; EAGLE Working Group, Genome-wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits, Biological Psychiatry, 2023
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