title: Common variation near ROBO2 is associated with expressive vocabulary in infancy.
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).
authors.affiliation: 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].
authors.forename: Beate
authors.initials: B
authors.lastname: St Pourcain
authors.affiliation: 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].
authors.forename: Rolieke A M
authors.initials: RA
authors.lastname: Cents
authors.affiliation: 1] Telethon Kids Institute, Centre for Child Health Research, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia [2].
authors.forename: Andrew J O
authors.initials: AJ
authors.lastname: Whitehouse
authors.affiliation: 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].
authors.forename: Claire M A
authors.initials: CM
authors.lastname: Haworth
authors.affiliation: 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].
authors.forename: Oliver S P
authors.initials: OS
authors.lastname: Davis
authors.affiliation: 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.
authors.forename: Paul F
authors.initials: PF
authors.lastname: O'Reilly
authors.affiliation: Bristol Speech and Language Therapy Research Unit, University of the West of England, Frenchay Hospital, Frenchay Park Road, BS16 1LE Bristol, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Roulstone
authors.affiliation: Bristol Speech and Language Therapy Research Unit, University of the West of England, Frenchay Hospital, Frenchay Park Road, BS16 1LE Bristol, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Wren
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, 374 Bagot Road, Subiaco, Western Australia 6008, Australia.
authors.forename: Qi W
authors.initials: QW
authors.lastname: Ang
authors.affiliation: 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.
authors.forename: Fleur P
authors.initials: FP
authors.lastname: Velders
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: 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.
authors.forename: John P
authors.initials: JP
authors.lastname: Kemp
authors.affiliation: 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.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: 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.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-University Medical Centre, Postbus 2060, 3000 CB Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: 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.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Psychological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Meaburn
authors.affiliation: Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 3400 Civic Center Boulevard, Building 421, Philadelphia, Pennsylvania 19104-5158, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Price
authors.affiliation: Department of Speech and Hearing Sciences, University of New Mexico, 1700 Lomas Boulevard NE Suite 1300, Albuquerque, New Mexico 87131, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Dale
authors.affiliation: 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.
authors.forename: Demetris
authors.initials: D
authors.lastname: Pillas
authors.affiliation: Faculty of Humanities, Logopedics, Child Language Research Center, University of Oulu, BOX 1000, Oulu 90014, Finland.
authors.forename: Anneli
authors.initials: A
authors.lastname: Yliherva
authors.affiliation: 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.
authors.forename: Alina
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.affiliation: 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.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: 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.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Plomin
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, 374 Bagot Road, Subiaco, Western Australia 6008, Australia.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.affiliation: 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].
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: 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.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
mesh_terms: D001321:Autistic Disorder / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D002874:Chromosome Mapping; D004410:Dyslexia / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007802:Language; D007804:Language Development; D007806:Language Disorders / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D011971:Receptors, Immunologic / Q000235:genetics*; D013060:Speech / Q000502:physiology; D066229:Speech Sound Disorder; D014825:Vocabulary; D044465:White People; D000097905:Roundabout Proteins
chemical_list: D011971:Receptors, Immunologic; C498890:ROBO2 protein, human; D000097905:Roundabout Proteins