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; EAGLE Working Group; Katherine Lange; Carol A. Wang; Angela T. 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; Consortium ACTION Consortium; Infant Study investigator group 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; Charlotte A.M. Cecil

doi:10.1016/j.biopsych.2023.11.025

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, EAGLE Working Group, Katherine Lange, Carol A. Wang, Angela T. 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 HoyosVincent 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, Consortium ACTION Consortium, Infant Study investigator group 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, Charlotte A.M. Cecil

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 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 (r_g) 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 (r_g = 0.07), although each measure was moderately related to toddler expressive vocabulary (r_g = 0.69 and r_g = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: r_g = 0.58 and r_g = 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: r_g = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (r_g = 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; r_g = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (r_g = −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.

Original language	English
Pages (from-to)	859-869
Number of pages	11
Journal	Biological Psychiatry
Volume	95
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2023.11.025
Publication status	Published - 1 May 2024

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Publisher Copyright:
© 2023 Society of Biological Psychiatry

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Verhoef, E., Allegrini, A. G., Jansen, P. R., EAGLE Working Group, Lange, K., Wang, C. A., Morgan, A. T., Ahluwalia, T. S., Symeonides, C., Andreassen, O. A., Bartels, M., Boomsma, D., Dale, P. S., Ehli, E., Fernandez-Orth, D., Guxens, M., Hakulinen, C., Harris, K. M., Haworth, S., ... Cecil, C. A. M. (2024). Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits. Biological Psychiatry, 95(9), 859-869. https://doi.org/10.1016/j.biopsych.2023.11.025

@article{6ab1bdf8bea145a4ade417e7272f4da2,

title = "Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits",

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 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.",

author = "Ellen Verhoef and Allegrini, {Andrea G.} and Jansen, {Philip R.} and {EAGLE Working Group} and Katherine Lange and Wang, {Carol A.} and Morgan, {Angela T.} and Ahluwalia, {Tarunveer S.} and Christos Symeonides and Andreassen, {Ole A.} and Meike Bartels and Dorret Boomsma and Dale, {Philip S.} and Erik Ehli and Dietmar Fernandez-Orth and M{\`o}nica Guxens and Christian Hakulinen and Harris, {Kathleen Mullan} and Simon Haworth and {de Hoyos}, Luc{\'i}a and Vincent Jaddoe and Liisa Keltikangas-J{\"a}rvinen and Terho Lehtim{\"a}ki and Christel Middeldorp and Min, {Josine L.} and Mishra, {Pashupati P.} and Nj{\o}lstad, {P{\aa}l Rasmus} and Jordi Sunyer and Tate, {Ashley E.} and Nicholas Timpson and {van der Laan}, Camiel and Martine Vrijheid and Eero Vuoksimaa and Alyce Whipp and Eivind Ystrom and {ACTION Consortium}, Consortium and {Barwon Infant Study investigator group}, {Infant Study investigator group} and Else Eising and Franken, {Marie Christine} and Elina Hypponen and Toby Mansell and Mitchell Olislagers and Emina Omerovic and Kaili Rimfeld and Fenja Schlag and Saskia Selzam and Shapland, {Chin Yang} and Henning Tiemeier and Whitehouse, {Andrew J.O.} and Richard Saffery and Cecil, {Charlotte A.M.}",

note = "Publisher Copyright: {\textcopyright} 2023 Society of Biological Psychiatry",

year = "2024",

month = may,

day = "1",

doi = "10.1016/j.biopsych.2023.11.025",

language = "English",

volume = "95",

pages = "859--869",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier Inc.",

number = "9",

}

Verhoef, E, Allegrini, AG, Jansen, PR, EAGLE Working Group, Lange, K, Wang, CA, Morgan, AT, Ahluwalia, TS, Symeonides, C, Andreassen, OA, Bartels, M, Boomsma, D, Dale, PS, Ehli, E, Fernandez-Orth, D, Guxens, M, Hakulinen, C, Harris, KM, Haworth, S, de Hoyos, L, Jaddoe, V, Keltikangas-Järvinen, L, Lehtimäki, T, Middeldorp, C, Min, JL, Mishra, PP, Njølstad, PR, Sunyer, J, Tate, AE, Timpson, N, van der Laan, C, Vrijheid, M, Vuoksimaa, E, Whipp, A, Ystrom, E, ACTION Consortium, C, Barwon Infant Study investigator group, ISIG, Eising, E, Franken, MC, Hypponen, E, Mansell, T, Olislagers, M, Omerovic, E, Rimfeld, K, Schlag, F, Selzam, S, Shapland, CY, Tiemeier, H, Whitehouse, AJO, Saffery, R & Cecil, CAM 2024, 'Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits', Biological Psychiatry, vol. 95, no. 9, pp. 859-869. https://doi.org/10.1016/j.biopsych.2023.11.025

Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits. / Verhoef, Ellen; Allegrini, Andrea G.; Jansen, Philip R. et al.
In: Biological Psychiatry, Vol. 95, No. 9, 01.05.2024, p. 859-869.

Research output: Contribution to journal › Article › Academic › peer-review

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 - EAGLE Working Group

AU - Lange, Katherine

AU - Wang, Carol A.

AU - Morgan, Angela T.

AU - Ahluwalia, Tarunveer S.

AU - Symeonides, Christos

AU - Andreassen, Ole A.

AU - Bartels, Meike

AU - Boomsma, Dorret

AU - Dale, Philip S.

AU - Ehli, Erik

AU - Fernandez-Orth, Dietmar

AU - Guxens, Mònica

AU - Hakulinen, Christian

AU - Harris, Kathleen Mullan

AU - Haworth, Simon

AU - de Hoyos, Lucía

AU - Jaddoe, Vincent

AU - Keltikangas-Järvinen, Liisa

AU - Lehtimäki, Terho

AU - Middeldorp, Christel

AU - Min, Josine L.

AU - Mishra, Pashupati P.

AU - Njølstad, Pål Rasmus

AU - Sunyer, Jordi

AU - Tate, Ashley E.

AU - Timpson, Nicholas

AU - van der Laan, Camiel

AU - Vrijheid, Martine

AU - Vuoksimaa, Eero

AU - Whipp, Alyce

AU - Ystrom, Eivind

AU - ACTION Consortium, Consortium

AU - Barwon Infant Study investigator group, Infant Study investigator group

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 - Cecil, Charlotte A.M.

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.

UR - http://www.scopus.com/inward/record.url?scp=85189155831&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2023.11.025

DO - 10.1016/j.biopsych.2023.11.025

M3 - Article

C2 - 38070845

AN - SCOPUS:85189155831

SN - 0006-3223

VL - 95

SP - 859

EP - 869

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 9

ER -

Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits

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