BackGenome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people
Eising, E., Mirza-Schreiber, N., de Zeeuw, E. L., Wang, C. A., Truong, D. T., Allegrini, A. G., . . .Carreiras, M., . . . Fisher, S. E. (2022). Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people. Proceedings of the National Academy of Sciences of the United States of America, 119(35):e2202764119. Doi:10.1073/pnas.2202764119
PNAS: PSYCHOLOGICAL AND COGNITIVE SCIENCES GENETICS
PNAS: PSYCHOLOGICAL AND COGNITIVE SCIENCES GENETICS
Abstract
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 × 1028) 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.