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

Background Reading 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. Methods We 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. Results Totally 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. Conclusions This 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was partially supported by a Collaborative Research Fund (CRF) (C4054-17W) from the Research Grants Council. HCS was also supported by the Lo Kwee Seong Biomedical Research Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has received ethics approval from the New Territories East Cluster (NTEC) of the Hospital Authority of Hong Kong (ref no: 2017.479). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.