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Verhoef, E, Allegrini, A G, Jansen, P R, EAGLE Working Group, Lange, K, Wang, C A, Morgan, A T, Ahluwalia, T S, Symeonides, C, Andreassen, O A, Bartels, M, Boomsma, D, Dale, P S, Ehli, E, Fernandez-Orth, D, Guxens, M, Hakulinen, C, Harris, K M, Haworth, S, de Hoyos, L, Jaddoe, V, Keltikangas-Järvinen, L, Lehtimäki, T, Middeldorp, C, Min, J L, Mishra, P P, Njølstad, P R, Sunyer, J, Tate, A E, Timpson, N, van der Laan, C, Vrijheid, M, Vuoksimaa, E, Whipp, A, Ystrom, E, ACTION Consortium, C, Barwon Infant Study investigator group, I S I G, Eising, .... |
| Description: |
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-h 2 ) and genetic correlations (r g ) and modeled underlying factor structures with multivariate models. Results: Early-life vocabulary size was modestly heritable (SNP-h 2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (r g = 0.07), although each measure was moderately related to toddler expressive vocabulary (r g = 0.69 and r g = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: r g = 0.58 and r g = 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: r g = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (r g = 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; r g = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (r g ... |