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Verhoef, Ellen; Allegrini, Andrea G.; Jansen, Philip R.; Lange, Katherine; Wang, Carol A.; Morgan, Angela T.; Ahluwalia, Tarunveer S.; Symeonides, Christos; EAGLE working group,; & Eising, Else, et al. (Online ahead of print). Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations with ADHD, Literacy and Cognition-Related Traits. Biological 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-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(g)=-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.


Reference Type

Journal Article

Year Published

Online ahead of print

Journal Title

Biological Psychiatry


Verhoef, Ellen
Allegrini, Andrea G.
Jansen, Philip R.
Lange, Katherine
Wang, Carol A.
Morgan, Angela T.
Ahluwalia, Tarunveer S.
Symeonides, Christos
EAGLE working group,
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 A.
Bartels, Meike
Boomsma, Dorret I.
Dale, Philip S.
Ehli, Erik A.
Fernandez-Orth, Dietmar
Guxens, Mònica
Hakulinen, Christian
Harris, Kathleen Mullan
Haworth, Simon
de Hoyos, Lucía
Jaddoe, Vincent W. V.
Keltikangas-Järvinen, Liisa
Lehtimäki, Terho
Middeldorp, Christel M.
Min, Josine L.
Mishra, Pashupati P.
Njølstad, Pål Rasmus
Sunyer, Jordi
Tate, Ashley E.
Timpson, Nicholas J.
van der Laan, Camiel
Vrijheid, Martine
Vuoksimaa, Eero
Whipp, Alyce
Ystrom, Eivind

Article Type


Data Set/Study

National Longitudinal Study of Adolescent to Adult Health (Add Health)


United States




Harris, KM - 0000-0001-9757-1026