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 and George Davey Smith
Additional contact information
Beate St Pourcain: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK
Rolieke A.M. Cents: Generation R Study Group, Erasmus MC-University Medical Centre
Andrew J.O. Whitehouse: Telethon Kids Institute, Centre for Child Health Research, University of Western Australia
Claire M.A. Haworth: University of Warwick
Oliver S.P. Davis: 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
Paul F. O’Reilly: 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
Susan Roulstone: Bristol Speech and Language Therapy Research Unit, University of the West of England, Frenchay Hospital
Yvonne Wren: Bristol Speech and Language Therapy Research Unit, University of the West of England, Frenchay Hospital
Qi W. Ang: School of Women’s and Infants’ Health, University of Western Australia
Fleur P. Velders: Generation R Study Group, Erasmus MC-University Medical Centre
David M. Evans: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK
John P. Kemp: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK
Nicole M. Warrington: School of Women’s and Infants’ Health, University of Western Australia
Laura Miller: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK
Nicholas J. Timpson: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK
Susan M. Ring: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK
Frank C. Verhulst: Erasmus MC-University Medical Centre
Albert Hofman: Erasmus MC-University Medical Centre
Fernando Rivadeneira: Erasmus MC-University Medical Centre
Emma L. Meaburn: Birkbeck, University of London
Thomas S. Price: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine
Philip S. Dale: University of New Mexico
Demetris Pillas: 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
Anneli Yliherva: Faculty of Humanities, Logopedics, Child Language Research Center, University of Oulu
Alina Rodriguez: 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
Jean Golding: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK
Vincent W.V. Jaddoe: Generation R Study Group, Erasmus MC-University Medical Centre
Marjo-Riitta Jarvelin: 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
Robert Plomin: 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
Craig E. Pennell: School of Women’s and Infants’ Health, University of Western Australia
Henning Tiemeier: Erasmus MC-University Medical Centre
George Davey Smith: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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’, NTotal=8,889) and a later (24–30 months, ‘two-word stage’, NTotal=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 h215–18-months=0.13, meta-GCTA h224–30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h224-months=0.20).

Date: 2014
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DOI: 10.1038/ncomms5831

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