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 T Morgan; Tarunveer S Ahluwalia; Christos Symeonides; EAGLE Working 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

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

Biol Psychiatry. 2024 May 1;95(9):859-869. doi: 10.1016/j.biopsych.2023.11.025. Epub 2023 Dec 7.

Authors

Ellen Verhoef¹, Andrea G Allegrini², Philip R Jansen³, Katherine Lange⁴, Carol A Wang⁵, Angela T Morgan⁶, Tarunveer S Ahluwalia⁷, Christos Symeonides⁸; EAGLE Working Group; Else Eising¹⁸, Marie-Christine Franken³¹, Elina Hypponen³², Toby Mansell⁴, Mitchell Olislagers³³, Emina Omerovic³⁴, Kaili Rimfeld³⁵, Fenja Schlag¹⁸, Saskia Selzam², Chin Yang Shapland³⁶, Henning Tiemeier³⁷, Andrew J O Whitehouse³⁸, Richard Saffery³⁹, Klaus Bønnelykke⁴⁰, Sheena Reilly⁴¹, Craig E Pennell⁴², Melissa Wake⁴³, Charlotte A M Cecil⁴⁴, Robert Plomin², Simon E Fisher⁴⁵, Beate St Pourcain⁴⁶

Collaborators

EAGLE Working Group:
Ole A Andreassen⁹, Meike Bartels¹⁰, Dorret Boomsma¹⁰, Philip S Dale¹¹, Erik Ehli¹², Dietmar Fernandez-Orth¹³, Mònica Guxens¹⁴, Christian Hakulinen¹⁵, Kathleen Mullan Harris¹⁶, Simon Haworth¹⁷, Lucía de Hoyos¹⁸, Vincent Jaddoe¹⁹, Liisa Keltikangas-Järvinen²⁰, Terho Lehtimäki²¹, Christel Middeldorp²², Josine L Min²³, Pashupati P Mishra²¹, Pål Rasmus Njølstad²⁴, Jordi Sunyer²⁵, Ashley E Tate²⁶, Nicholas Timpson²³, Camiel van der Laan¹⁰, Martine Vrijheid²⁵, Eero Vuoksimaa²⁷, Alyce Whipp²⁷, Eivind Ystrom²⁸, Action Consortium²⁹, Barwon Infant Study Investigator Group³⁰

Affiliations

¹ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands. Electronic address: ellen.verhoef@mpi.nl.
² Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, the Netherlands; Section Clinical Genetics, Department Human Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
⁴ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
⁵ School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia; Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁶ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Department of Audiology and Speech Pathology, University of Melbourne, Parkville, Victoria, Australia; Royal Children's Hospital, Melbourne, Victoria, Australia.
⁷ Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Herlev, Denmark; Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
⁸ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Royal Children's Hospital, Melbourne, Victoria, Australia; Minderoo Foundation, Perth, Western Australia, Australia.
⁹ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway.
¹⁰ Netherlands Twin Register, dept Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
¹¹ Speech & Hearing Sciences Department, University of New Mexico, Albuquerque, New Mexico.
¹² Avera Institute for Human Genetics, Sioux Falls, South Dakota.
¹³ ISGlobal, Barcelona, Spain.
¹⁴ ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, University Medical Centre, Rotterdam, the Netherlands.
¹⁵ Department of Psychology and Logopedics, University of Helsinki, Finland.
¹⁶ Department of Sociology, University of North Carolina at Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina at Chapel Hill, North Carolina.
¹⁷ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, England, UK; Bristol Dental School, University of Bristol, Bristol, England, UK.
¹⁸ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
¹⁹ Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
²⁰ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²¹ Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
²² University of Queensland, Child health Research Centre, Brisbane, Queensland, Australia; Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia.
²³ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, England, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
²⁴ Department of Clinical Science, University of Bergen, Bergen, Norway; Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway.
²⁵ ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain.
²⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁷ Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
²⁸ PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway; Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
²⁹ Supplemental Note, ACTION Consortium Genome-wide-Association Meta-analysis authors and affiliations.
³⁰ Supplemental Note, Barwon Infant Study investigator group authors and affiliations.
³¹ Erasmus University Medical Center, Sophia Children's Hospital, Department of Otorhinolaryngology and Head and Neck Surgery, Rotterdam, the Netherlands.
³² Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
³³ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Department of Urology, Erasmus University Medical Center, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.
³⁴ Murdoch Children's Research Institute, Parkville, Victoria, Australia.
³⁵ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychology, Royal Holloway University of London, London, UK.
³⁶ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, University of Bristol, Bristol, UK.
³⁷ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands; Harvard, T.H. Chan School of Public Health, Boston, Massachusetts.
³⁸ Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
³⁹ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Chongqing Medical University, Chongqing, China.
⁴⁰ Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
⁴¹ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Menzies Health Institute Queensland, Griffith University, Brisbane, Queensland, Australia.
⁴² School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia; Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Maternity and Gynaecology John Hunter Hospital, Newcastle, New South Wales, Australia.
⁴³ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Liggins Institute, The University of Auckland, Grafton, New Zealand.
⁴⁴ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
⁴⁵ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
⁴⁶ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. Electronic address: Beate.StPourcain@mpi.nl.

PMID: 38070845
DOI: 10.1016/j.biopsych.2023.11.025

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.

Keywords: ADHD; Cognition; Development; GWAS; SEM; Vocabulary.

Publication types

Meta-Analysis

MeSH terms

Adolescent
Attention Deficit Disorder with Hyperactivity* / diagnosis
Attention Deficit Disorder with Hyperactivity* / genetics
Cognition
Genome-Wide Association Study
Humans
Infant
Literacy*
Longitudinal Studies
Phenotype
Vocabulary