Genome-wide analyses of vocabulary size in infancy and toddlerhood: associations with ADHD, literacy and cognition-related traits
Verhoef, Ellen; Allegrini, Andrea G.; Jansen, Philip R.; Lange, Katherine; Wang, Carol A.; Morgan, Angela; Ahluwalia, Tarunveer S.; Symeonides, Christos; 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; Andreassen, Ole; Bartels, Meike; Boomsma, Dorret; Dale, Philip S.; Ehli, Erik; Fernandez-Orth, Dietmar; Guxens, Mònica; Hakulinen, Christian; Harris, Kathleen Mullan; Haworth, Simon; de Hoyos, Lucía; Jaddoe, Vincent; Keltikangas-Järvinen, Liisa; Lehtimäki, Terho; Middeldorp, Christel; Min, Josine L.; Mishra, Pashupati P.; Njølstad, Pål Rasmus; Sunyer, Jordi; Tate, Ashley E.; Timpson, Nicholas; van der Laan, Camiel; Vrijheid, Martine; Vuoksimaa, Eero; Whipp, Alyce M.; Ystrøm, Eivind
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Date
2024Metadata
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- Department of Clinical Science [2374]
- Registrations from Cristin [10149]
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.