Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits
Ellen Verhoef, Andrea G. Allegrini, Philip R. Jansen, Katherine Lange, Carol A. Wang, Angela Morgan, Tarunveer S. Ahluwalia, Christos Symeonides, Ole A. Andreassen, Meike Bartels, Dorret Boomsma, Philip S. Dale, Erik Ehli, Dietmar Fernandez-Orth, Mònica Guxens, Christian Hakulinen, Kathleen Mullan Harris, Simon Haworth, Lucía de Hoyos, Vincent Jaddoe, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Christel Middeldorp, Josine L. Min, Pashupati P. Mishra, Pål Rasmus Njølstad, Jordi Sunyer, Ashley E. Tate, Nicholas Timpson, Camiel van der Laan, Martine Vrijheid, Eero Vuoksimaa, Alyce Whipp, Eivind Ystrom, Barwon Infant Study investigator group, Else Eising, Marie-Christine Franken, Elina Hypponen, Toby Mansell, Mitchell Olislagers, Emina Omerovic, Kaili Rimfeld, Fenja Schlag, Saskia Selzam, Chin Yang Shapland, Henning Tiemeier, Andrew J.O. Whitehouse, Richard Saffery, Klaus Bønnelykke, Sheena Reilly, Craig E. Pennell, Melissa Wake, Charlotte A.M. Cecil, Robert Plomin, Simon E. Fisher, Beate St. Pourcain
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 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.