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

Verhoef, E., Allegrini, A. G., Jansen, P. R., Lange, K., Wang, C. A., Morgan, A. T., Ahluwalia, T. S., Symeonides, C., EAGLE-Working Group, Eising, E., Franken, M.-C., Hypponen, E., Mansell, T., Olislagers, M., Omerovic, E., Rimfeld, K., Schlag, F., Selzam, S., Shapland, C. Y., Tiemeier, H., Whitehouse, A. J. O. Verhoef, E., Allegrini, A. G., Jansen, P. R., Lange, K., Wang, C. A., Morgan, A. T., Ahluwalia, T. S., Symeonides, C., EAGLE-Working Group, Eising, E., Franken, M.-C., Hypponen, E., Mansell, T., Olislagers, M., Omerovic, E., Rimfeld, K., Schlag, F., Selzam, S., Shapland, C. Y., Tiemeier, H., Whitehouse, A. J. O., Saffery, R., Bønnelykke, K., Reilly, S., Pennell, C. E., Wake, M., Cecil, C. A., Plomin, R., Fisher, S. E., & St Pourcain, B. (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.
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.
Publication type
Journal article
Publication date
2023

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