A genome-wide association study of Chinese and English language abilities in Hong Kong Chinese children

BackgroundReading and language skills are important and known to be heritable, and dyslexia and developmental language disorder are commonly recognized learning difficulties worldwide. However, the genetic basis underlying these skills remains poorly understood. In particular, most previous genetic studies were performed on Westerners. To our knowledge, few or no previous genome-wide association studies (GWAS) have been conducted on literacy skills in Chinese as a native language or English as a second language (ESL) in a Chinese population. MethodsWe conducted GWAS and related bioinformatics analyses on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; N=1046). We performed association tests at the single-variant, gene, pathway levels, and transcriptome-wide association studies (TWAS) to explore how imputed expression changes might affect the phenotypes. In addition, we tested genetic overlap of these cognitive traits with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. ResultsTotally 9 independent loci (LD-clumped at r2=0.01) reached genome-wide significance (p<5e-08) (filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs(r2>0.5) with p<1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, dictation and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with intelligence, EA other neuropsychiatric phenotypes, such as MANEA, TNR, PLXNC1 and SHTN1. We also revealed significantly enriched genes and pathways based on SNP-based analysis. In PRS analysis, EA and CP showed significant polygenic overlap with a variety of language traits, especially English literacy skills. ADHD PRS showed a significant association with English vocabulary score. ConclusionsThis study revealed numerous genetic loci that may be associated with Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings and elucidate the mechanisms involved.