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 - EAGLE Working Group
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
N1 - Publisher Copyright:
© 2023 Society of Biological Psychiatry
PY - 2024/5/1
Y1 - 2024/5/1
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 - Adolescent
KW - Humans
KW - Infant
KW - Attention Deficit Disorder with Hyperactivity/genetics
KW - Cognition
KW - Genome-Wide Association Study
KW - Literacy
KW - Longitudinal Studies
KW - Phenotype
KW - Vocabulary
U2 - 10.1016/j.biopsych.2023.11.025
DO - 10.1016/j.biopsych.2023.11.025
M3 - Article (Academic Journal)
C2 - 38070845
SN - 0006-3223
VL - 95
SP - 859
EP - 869
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -