Common variation near ROBO2 is associated with expressive vocabulary in infancy

Beate St Pourcain; Rolieke A M Cents; Andrew J O Whitehouse; Claire M A Haworth; Oliver S P Davis; Paul F O'Reilly; Susan Roulstone; Yvonne Wren; Qi W Ang; Fleur P Velders; David M Evans; John P Kemp; Nicole M Warrington; Laura Miller; Nicholas J Timpson; Susan M Ring; Frank C Verhulst; Albert Hofman; Fernando Rivadeneira; Emma L Meaburn; Thomas S Price; Philip S Dale; Demetris Pillas; Anneli Yliherva; Alina Rodriguez; Jean Golding; Vincent W V Jaddoe; Marjo-Riitta Jarvelin; Robert Plomin; Craig E Pennell; Henning Tiemeier; George Davey Smith

doi:10.1038/ncomms5831

Common variation near ROBO2 is associated with expressive vocabulary in infancy

Nat Commun. 2014 Sep 16:5:4831. doi: 10.1038/ncomms5831.

Authors

Beate St Pourcain¹, Rolieke A M Cents², Andrew J O Whitehouse³, Claire M A Haworth⁴, Oliver S P Davis⁵, Paul F O'Reilly⁶, Susan Roulstone⁷, Yvonne Wren⁷, Qi W Ang⁸, Fleur P Velders⁹, David M Evans¹⁰, John P Kemp¹⁰, Nicole M Warrington¹¹, Laura Miller¹², Nicholas J Timpson¹³, Susan M Ring¹³, Frank C Verhulst¹⁴, Albert Hofman¹⁵, Fernando Rivadeneira¹⁶, Emma L Meaburn¹⁷, Thomas S Price¹⁸, Philip S Dale¹⁹, Demetris Pillas²⁰, Anneli Yliherva²¹, Alina Rodriguez²², Jean Golding¹², Vincent W V Jaddoe²³, Marjo-Riitta Jarvelin²⁴, Robert Plomin²⁵, Craig E Pennell⁸, Henning Tiemeier²⁶, George Davey Smith¹³

Affiliations

¹ 1] Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK [2] School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK [3] School of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK [4].
² 1] Generation R Study Group, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands [3].
³ 1] Telethon Kids Institute, Centre for Child Health Research, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia [2].
⁴ 1] Department of Psychology, University of Warwick, Coventry CV4 7AL, UK [2] Medical Research Council, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK [3].
⁵ 1] Medical Research Council, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK [2] Department of Genetics, Evolution and Environment, UCL, UCL Genetics Institute, Darwin Building, Gower Street, London WC1E 6BT, UK [3].
⁶ 1] Medical Research Council, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK [2] Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
⁷ Bristol Speech and Language Therapy Research Unit, University of the West of England, Frenchay Hospital, Frenchay Park Road, BS16 1LE Bristol, UK.
⁸ School of Women's and Infants' Health, University of Western Australia, 374 Bagot Road, Subiaco, Western Australia 6008, Australia.
⁹ 1] Generation R Study Group, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands.
¹⁰ 1] Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK [2] School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK [3] University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, 37 Kent Street Woolloongabba, Queensland 4102, Australia.
¹¹ 1] School of Women's and Infants' Health, University of Western Australia, 374 Bagot Road, Subiaco, Western Australia 6008, Australia [2] University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, 37 Kent Street Woolloongabba, Queensland 4102, Australia.
¹² School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
¹³ 1] Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK [2] School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
¹⁴ Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands.
¹⁵ Department of Epidemiology, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
¹⁶ 1] Department of Epidemiology, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Internal Medicine, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
¹⁷ Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
¹⁸ Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 3400 Civic Center Boulevard, Building 421, Philadelphia, Pennsylvania 19104-5158, USA.
¹⁹ Department of Speech and Hearing Sciences, University of New Mexico, 1700 Lomas Boulevard NE Suite 1300, Albuquerque, New Mexico 87131, USA.
²⁰ Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
²¹ Faculty of Humanities, Logopedics, Child Language Research Center, University of Oulu, BOX 1000, Oulu 90014, Finland.
²² 1] Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK [2] Mid Sweden University Department for Psychology/Mittuniversitetet Avdelningen för psykologi, 83125 Östersund, Sweden.
²³ 1] Generation R Study Group, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [3] Department of Pediatrics, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands.
²⁴ 1] Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK [2] Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, PO Box 20, FI-90220, Oulu 90029, Finland [3] Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland [4] Institute of Health Sciences, University of Oulu, PO Box 5000, Oulu FI-90014, Finland [5] Biocenter Oulu, University of Oulu, PO Box 5000, Aapistie 5A, OuluFI-90014, Finland.
²⁵ Medical Research Council, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
²⁶ 1] Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands [3].

Abstract

Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15-18 months, 'one-word stage', N(Total) = 8,889) and a later (24-30 months, 'two-word stage', N(Total)=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10(-8)) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h(2)(15-18-months) = 0.13, meta-GCTA h(2)(24-30-months) = 0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h(2)(24-months) = 0.20).

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autistic Disorder / ethnology
Autistic Disorder / genetics*
Autistic Disorder / physiopathology
Child, Preschool
Chromosome Mapping
Dyslexia / ethnology
Dyslexia / genetics*
Dyslexia / physiopathology
Female
Gene Expression
Genetic Linkage
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Infant
Language
Language Development*
Language Disorders / ethnology
Language Disorders / genetics*
Language Disorders / physiopathology
Male
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci*
Receptors, Immunologic / genetics*
Speech / physiology
Speech Sound Disorder
Vocabulary
White People

Common variation near ROBO2 is associated with expressive vocabulary in infancy

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