Common variation near ROBO2 is associated with expressive vocabulary in infancy

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

Abstract

© 2014 Macmillan Publishers Limited. All rights reserved. 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).

• Journal Article Type: Article
• Publication Date: Sep 16, 2014
• Deposit Date: Dec 15, 2014
• Publicly Available Date: Apr 4, 2016
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Research (part of Springer Nature)
• Peer Reviewed: Peer Reviewed
• Volume: 5
• DOI: https://doi.org/10.1038/ncomms5831
• Keywords: common variation, ROBO2, vocabulary, infancy
• Public URL: https://uwe-repository.worktribe.com/output/813161
• Publisher URL: http://dx.doi.org/10.1038/ncomms5831
• Contract Date: Apr 4, 2016