Genome-wide analyses of vocabulary size in infancy and toddlerhood: 
Associations with Attention-Deficit/Hyperactivity Disorder and 
cognition-related traits

Verhoef, Ellen; Allegrini, Andrea G.; Jansen, Philip R.; Lange, Katherine; Wang, Carol A.; Morgan, Angela T.; Ahluwalia, Tarunveer S.; Symeonides, Christos; EAGLE Working Group; Eising, Else; Franken, Marie-Christine; Hypponen, Elina; Mansell, Toby; Olislagers, Mitchell; Omerovic, Emina; Rimfeld, Kaili; Schlag, Fenja; Selzam, Saskia; Shapland, Chin Yang; Tiemeier, Henning; Whitehouse, Andrew J. O.; Saffery, Richard; Bønnelykke, Klaus; Reilly, Sheena; Pennell, Craig E.; Wake, Melissa; Cecil, Charlotte A.M.; Plomin, Robert; Fisher, Simon E.; St Pourcain, Beate

doi:10.1016/j.biopsych.2023.11.025

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Genome-wide analyses of vocabulary size in infancy and toddlerhood: Associations with Attention-Deficit/Hyperactivity Disorder and cognition-related traits

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Verhoef, Ellen
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society;

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Eising, Else
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;

Olislagers, Mitchell
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Erasmus University Medical Center;

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Schlag, Fenja
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society;

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Fisher, Simon E.
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;

/persons/resource/persons180748

St Pourcain, Beate
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society;
University of Bristol;
Donders Institute for Brain, Cognition and Behaviour, External Organizations;

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Citation

Verhoef, E., Allegrini, A. G., Jansen, P. R., Lange, K., Wang, C. A., Morgan, A. T., et al. (2023). Genome-wide analyses of vocabulary size in infancy and toddlerhood: Associations with Attention-Deficit/Hyperactivity Disorder and cognition-related traits. Biological Psychiatry. Advance online publication. doi:10.1016/j.biopsych.2023.11.025.

Cite as: https://hdl.handle.net/21.11116/0000-000E-0167-D

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.