Genomic contributions to infant and toddler vocabulary scores: Implications for association with health-, cognition-, and behaviour-related outcomes

Importance The number of words a child produces (expressive vocabulary) and understands (receptive vocabulary) change rapidly during infancy and toddlerhood, partially due to genetic factors. However, the genetic architecture underlying vocabulary development and association patterns with later-life outcomes, have not yet been fully characterised. Objective To (i) study the multivariate genetic architecture underlying vocabulary size during infancy and toddlerhood, and (ii) describe polygenic association patterns with childhood behavioural and health measures, as well as adult cognition-related outcomes. Design Meta-genome-wide association study (meta-GWAS) of expressive and receptive vocabulary (age: 15-38 months) performed within the Early Genetics and Life Course Epidemiology (EAGLE) Consortium. Structural equation modelling techniques were applied to study multivariate genetic architectures. Setting Children of European descent across seven independent population-based cohorts. Participants 37,913 observations from 17,298 individuals. Main Outcome and Measure Meta-analyses were performed for early-phase expressive vocabulary (15-18 months), late-phase expressive vocabulary (24-38 months), late-phase receptive vocabulary (24-38 months), and combinations thereof. Vocabulary size was assessed by parent report using standardised psychological instruments. Results Common genetic variation explained a modest proportion of phenotypic variation across all vocabulary measures (Single-Nucleotide Polymorphism heritability: 0.08(SE=0.01) to 0.24(SE=0.03)). Genetic correlation (rg) analyses showed that late-phase expressive vocabulary largely shared genetic influences with both early-phase expressive (rg=0.69(SE=0.14)) and late-phase receptive vocabulary (rg=0.67(SE=0.16)). However, the latter two measures were genetically unrelated (rg=0.07(SE=0.10)), suggesting different underlying genetic factors. Consistently, we observed differences in polygenic association patterns: Larger early-phase expressive vocabulary size was genetically correlated with increased ADHD risk (rg=0.23(SE=0.08)) and childhood maltreatment exposure (rg=0.19(SE=0.07)), a behavioural proxy. In contrast, larger late-phase receptive vocabulary size was genetically correlated with lower childhood maltreatment exposure (rg=-0.33(SE=0.08)). Finally, toddler, but not infant, vocabulary size was linked to cognitive skills (e.g. late-phase expressive vocabulary and intelligence: rg=0.32(SE=0.08)), despite comparable power. Conclusions and Relevance There are at least two distinct genetic components contributing to vocabulary development during infancy and toddlerhood that shape polygenic association patterns with later-life cognition and ADHD-related traits. Our findings suggest differences in biological mechanisms during a phase where children “learn to speak” (infancy) compared to a phase where children mastered some fluency and “speak to learn” (toddlerhood). Question What is the genetic architecture underlying vocabulary acquisition during language development, and does it affect links with later-life outcomes? Findings At least two genetic components contribute to vocabulary size, predominantly distinguishing infant expressive from toddler receptive vocabulary. Matching patterns of genetic overlap were found with later-life outcomes: Larger infant expressive but smaller toddler receptive vocabulary size was correlated with higher ADHD risk and/or childhood maltreatment exposure (a behavioural proxy). Consistently, later-life cognition was associated with toddler vocabulary scores only, irrespective of power. Meaning The genetic architecture underlying vocabulary acquisition is dynamic, shaping polygenic associations with later-life behaviour and cognition. ### Competing Interest Statement OAA is a consultant to HealthLytix. All other authors declare no conflict of interest.