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 › peer-review

61 Citations (Scopus)

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', 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 h_15-18-months₂=0.13, meta-GCTA h_24-30-months₂ =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h_24-months₂=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

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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., ... Smith, G. D. (2014). Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Communications, 5, Article 4831. https://doi.org/10.1038/ncomms5831

@article{43b15203f894412bafca56a80a48ecae,

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', 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 h15-18-months2=0.13, meta-GCTA h24-30-months2 =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h24-months2=0.20).",

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 Jarvelin, {Marjo Riitta} and Robert Plomin and Pennell, {Craig E.} and Henning Tiemeier and Smith, {George Davey}",

year = "2014",

month = sep,

day = "16",

doi = "10.1038/ncomms5831",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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}

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, MR, Plomin, R, Pennell, CE, Tiemeier, H & Smith, GD 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 - Smith, George Davey

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', 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 h15-18-months2=0.13, meta-GCTA h24-30-months2 =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h24-months2=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', 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 h15-18-months2=0.13, meta-GCTA h24-30-months2 =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h24-months2=0.20).

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U2 - 10.1038/ncomms5831

DO - 10.1038/ncomms5831

M3 - Article

C2 - 25226531

AN - SCOPUS:84910107464

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

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