Genetic variants in the CNTNAP2 gene are associated with gender differences among dyslexic children in China

BACKGROUND: It is well known that males have a higher prevalence of developmental dyslexia (DD) than females. Although the mechanism underlying this gender difference remains unknown, the contactin-associated protein-like 2 (CNTNAP2) gene, which shows sex-specific patterns in some neurodevelopmental disorders, has attracted extensive attention. This study aimed to explore whether CNTNAP2 shows a sex-specific association with DD in a Chinese population. METHODS: Using genomic DNA samples of 726 students [372 cases (282 male, 90 female), 354 controls (267 male, 87 female)], we genotyped five SNPs of CNTNAP2. Gender-stratified logistic regression models were used to determine the relationships between the CNTNAP2 variants and DD. FINDINGS: After adjustment for the false discovery rate (FDR), two SNPs (rs3779031, rs987456) of CNTNAP2 were associated with DD risk in females but not in males. Female participants carrying the rs3779031 G allele had a lower risk of DD than those with the A genotype [GG vs AA: OR (95%CI) = 0.281 (0.097–0.814)]. The rs987456 CC genotype was associated with a decreased risk of DD in females [CC vs AA+CA: OR (95%CI) = 0.222 (0.078–0.628)]. Furthermore, the interaction between CNTNAP2 (rs987456) and environmental factors (scheduled reading time) played a protective role in females [OR (95%CI) = 0.431 (0.188–0.987)]. INTERPRETATION: We performed a genetic association study on CNTNAP2 variants and DD. The sex specificity of CNTNAP2 in DD, along with the gene-environment interaction may help us to understand gender differences in DD.