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).