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-h 2) and genetic correlations (r g), and modelled underlying factor structures with multivariate models. RESULTS: Early-life vocabulary size was modestly heritable (SNP-h 2: 0.08(SE=0.01) to 0.24(SE=0.03)). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (r g=0.07(SE=0.10)), although each measure was moderately related to toddler expressive vocabulary (r g=0.69(SE=0.14) and r g=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: r g=0.58(SE=0.20) and r g=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: r g=0.36(SE=0.12)). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (r g=0.23(SE=0.08)). Multivariate genetic models in the ALSPAC cohort confirmed this finding for ADHD symptoms (r g=0.54(SE=0.26)), but showed that the association effect reversed for toddler receptive vocabulary (r ...