LAUSR

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.