The use of spoken and written language is a fundamental human capacity. Individual
differences in reading- and language-related skills are influenced by genetic variation,
with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic
architecture is complex, heterogeneous, and multifactorial, but investigations of
contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered.
We present a multicohort genome-wide association study (GWAS) of five traits assessed
individually using psychometric measures (word reading, nonword reading, spelling,
phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants
aged 5 to 26 y. We identified genome-wide significant association with word reading
(rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence
or educational attainment. All five reading-/language-related traits showed robust
SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural
equation modeling revealed a shared genetic factor explaining most of the variation
in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped
with genetic variation contributing to nonword repetition, intelligence, and educational
attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness
maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging
traits identified an association with the surface area of the banks of the left superior
temporal sulcus, a brain region linked to the processing of spoken and written language.
Heritability was enriched for genomic elements regulating gene expression in the fetal
brain and in chromosomal regions that are depleted of Neanderthal variants. Together,
these results provide avenues for deciphering the biological underpinnings of uniquely
human traits.
