TY - JOUR

T1 - Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood

T2 - Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits

AU - Verhoef, Ellen

AU - Allegrini, Andrea G.

AU - Jansen, Philip R.

AU - Lange, Katherine

AU - Wang, Carol A.

AU - Morgan, Angela T.

AU - Ahluwalia, Tarunveer S.

AU - Symeonides, Christos

AU - Eising, Else

AU - Franken, Marie-Christine

AU - Hypponen, Elina

AU - Mansell, Toby

AU - Olislagers, Mitchell

AU - Omerovic, Emina

AU - Rimfeld, Kaili

AU - Schlag, Fenja

AU - Selzam, Saskia

AU - Shapland, Chin Yang

AU - Tiemeier, Henning

AU - Whitehouse, Andrew J.O.

AU - Saffery, Richard

AU - Bønnelykke, Klaus

AU - Reilly, Sheena

AU - Pennell, Craig E

AU - Wake, Melissa

AU - Cecil, Charlotte A.M.

AU - Plomin, Robert

AU - Fisher, Simon E.

AU - St Pourcain, Beate

AU - EAGLE Working Group

AU - ACTION consortium

AU - Barwon Infant Study Investigator Group

N1 - Publisher Copyright: © 2023 Society of Biological Psychiatry

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - ADHD

KW - Cognition

KW - Development

KW - GWAS

KW - SEM

KW - Vocabulary

U2 - 10.1016/j.biopsych.2023.11.025

DO - 10.1016/j.biopsych.2023.11.025

M3 - Journal article

C2 - 38070845

AN - SCOPUS:85189155831

VL - 95

SP - 859

EP - 869

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 9

ER -