Dyslexia is a common neurodevelopmental disorder, but its underlying mechanisms remain unclear. Based on the Tongji Reading Environment and Dyslexia (READ) project, this study aimed to evaluate the associations of solute carrier (SLC) gene polymorphisms and heavy metal exposure with dyslexia in Chinese children and to further explore gene-environment interactions. Dyslexia was screened using the Dyslexia Checklist for Chinese Children and the Pupil Rating Scale-Revised Screening. Bioinformatics strategy was used to identify functional SLC-related SNPs, and genotyping was performed using the ASAMD array. Urinary heavy metal concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Five functional SLC-related SNPs were associated with dyslexia risk, and SLC22A3 rs555754 remained significant after multiple-testing correction (OR = 1.37; 95% CI, 1.11–1.69; P FDR = 0.045). In addition, higher urinary barium and strontium levels were associated with increased dyslexia risk, and barium showed a U-shaped nonlinear association with dyslexia. In gene-environment analyses, a multiplicative interaction was observed between barium and SLC18A2 rs2619095 ( P mul = 0.041). Compared with children with low barium exposure and the rs2619095 CC genotype, those with high barium exposure and the CA/AA genotype had 2.41-fold higher odds of dyslexia (OR = 2.41; 95% CI, 1.35–4.29). Overall, this is the first study to link SLC polymorphisms and multiple metal exposures to dyslexia in children. Our findings suggest that genetic and environmental factors may jointly influence dyslexia risk, providing new epidemiologic evidence and clues to advance understanding of dyslexia pathogenesis. • First study linking SLC-SNPs and multiple metal exposures to dyslexia in children. • The rs555754 SNP in SLC22A3 is associated with the risk of dyslexia. • Urinary barium level exhibits a U-shaped association with dyslexia risk. • A novel interaction exists between rs2619095 and barium.
Zeng et al. (Sun,) studied this question.