Genome-wide analyses of vocabulary size in infancy and toddlerhood: associations with ADHD, literacy and cognition-related traits

TitleGenome-wide analyses of vocabulary size in infancy and toddlerhood: associations with ADHD, literacy and cognition-related traits
Publication TypeJournal Article
Year of Publication2023
AuthorsVerhoef, E, Allegrini, AG, Jansen, PR, Lange, K, Wang, CA, Morgan, AT, Ahluwalia, TS, Symeonides, C, Eising, E, Franken, M-C, Hypponen, E, Mansell, T, Olislagers, M, Omerovic, E, Rimfeld, K, Schlag, F, Selzam, S, Shapland, CYang, Tiemeier, H, Whitehouse, AJO, Saffery, R, Bønnelykke, K, Reilly, S, Pennell, CE, Wake, M, Cecil, CAM, Plomin, R, Fisher, SE, St Pourcain, B, Andreassen, OA, Bartels, M, Boomsma, D, Dale, PS, Ehli, E, Fernandez-Orth, D, Guxens, M, Hakulinen, C, Harris, KMullan, Haworth, S, de Hoyos, L, Jaddoe, V, Keltikangas-Järvinen, L, Lehtimäki, T, Middeldorp, C, Min, JL, Mishra, PP, Njølstad, P\aalRasmus, Sunyer, J, Tate, AE, Timpson, N, van der Laan, C, Vrijheid, M, Vuoksimaa, E, Whipp, A, Ystrom, E
JournalBiological Psychiatry
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 European descent children. 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 heritability (SNP-h2) and genetic correlations (rg), and modelled underlying factor structures with multivariate models.
RESULTS. Early-life vocabulary size was modestly heritable (SNP-h2: 0.08(SE=0.01) to 0.24(SE=0.03)). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg=0.07(SE=0.10)), although each measure was moderately related to toddler expressive vocabulary (rg=0.69(SE=0.14) and rg=0.67(SE=0.16), respectively), suggesting a multi-factorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g. spelling: rg=0.58(SE=0.20) and rg=0.79(SE=0.25), respectively), underlining genetic similarity. However, genetic association of early-life vocabulary with educational attainment and intelligence emerged in toddlerhood only (e.g. receptive vocabulary and intelligence: rg=0.36(SE=0.12)). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg=0.23(SE=0.08)). Multivariate genetic models in the ALSPAC cohort confirmed this finding for ADHD symptoms (rg=0.54(SE=0.26)), but showed that the association effect reversed for toddler receptive vocabulary (rg=-0.74(SE=0.23)), 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.