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

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 MeaburnThomas 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

^*Corresponding author for this work

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

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).

Original language	English
Article number	4831
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5831
Publication status	Published - 16 Sept 2014
Externally published	Yes

Keywords

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

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10.1038/ncomms5831

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St Pourcain, B., Cents, R. A. M., Whitehouse, A. J. O., Haworth, C. M. A., Davis, O. S. P., O'Reilly, P. F., Roulstone, S., Wren, Y., Ang, Q. W., Velders, F. P., Evans, D. M., Kemp, J. P., Warrington, N. M., Miller, L., Timpson, N. J., Ring, S. M., Verhulst, F. C., Hofman, A., Rivadeneira, F., ... Davey Smith, G. (2014). Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Communications, 5, Article 4831. https://doi.org/10.1038/ncomms5831

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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).",

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

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

year = "2014",

month = sep,

day = "16",

doi = "10.1038/ncomms5831",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

St Pourcain, B, Cents, RAM, Whitehouse, AJO, Haworth, CMA, Davis, OSP, O'Reilly, PF, Roulstone, S, Wren, Y, Ang, QW, Velders, FP, Evans, DM, Kemp, JP, Warrington, NM, Miller, L, Timpson, NJ, Ring, SM, Verhulst, FC, Hofman, A, Rivadeneira, F, Meaburn, EL, Price, TS, Dale, PS, Pillas, D, Yliherva, A, Rodriguez, A, Golding, J, Jaddoe, VWV, Jarvelin, M-R, Plomin, R, Pennell, CE, Tiemeier, H & Davey Smith, G 2014, 'Common variation near ROBO2 is associated with expressive vocabulary in infancy', Nature Communications, vol. 5, 4831. https://doi.org/10.1038/ncomms5831

TY - JOUR

T1 - Common variation near ROBO2 is associated with expressive vocabulary in infancy

AU - St Pourcain, Beate

AU - Cents, Rolieke A M

AU - Whitehouse, Andrew J O

AU - Haworth, Claire M A

AU - Davis, Oliver S P

AU - O'Reilly, Paul F

AU - Roulstone, Susan

AU - Wren, Yvonne

AU - Ang, Qi W

AU - Velders, Fleur P

AU - Evans, David M

AU - Kemp, John P

AU - Warrington, Nicole M

AU - Miller, Laura

AU - Timpson, Nicholas J

AU - Ring, Susan M

AU - Verhulst, Frank C

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Meaburn, Emma L

AU - Price, Thomas S

AU - Dale, Philip S

AU - Pillas, Demetris

AU - Yliherva, Anneli

AU - Rodriguez, Alina

AU - Golding, Jean

AU - Jaddoe, Vincent W V

AU - Jarvelin, Marjo-Riitta

AU - Plomin, Robert

AU - Pennell, Craig E

AU - Tiemeier, Henning

AU - Davey Smith, George

PY - 2014/9/16

Y1 - 2014/9/16

N2 - 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).

AB - 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).

KW - Autistic Disorder/ethnology

KW - Child, Preschool

KW - Chromosome Mapping

KW - Dyslexia/ethnology

KW - Female

KW - Gene Expression

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Infant

KW - Language

KW - Language Development

KW - Language Disorders/ethnology

KW - Male

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Receptors, Immunologic/genetics

KW - Speech/physiology

KW - Speech Sound Disorder

KW - Vocabulary

KW - White People

U2 - 10.1038/ncomms5831

DO - 10.1038/ncomms5831

M3 - Article

C2 - 25226531

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4831

ER -

Common variation near ROBO2 is associated with expressive vocabulary in infancy

Abstract

Keywords

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