Environmental factors and polygenic risk score for psychiatric and neurodevelopmental disorders in children with dyslexia

Developmental dyslexia (DD) impacts learning achievement and psychosocial development and is associated with various environmental factors and also genetic factors. Here, we conducted a multi-center case-control study by screening 29,820 primary school students between 2–6 grades in four cities in China and enrolled 948 dyslexia cases who meet the criteria of dyslexia and 948 controls with matching age and sex. We comprehensively investigated the environmental factors using the eXtreme Gradient Boosting (XGBoost) machine learning model and Shapley additive explanations (SHAP) algorithm. The most important risk factors in dyslexia are the proactive learning habit, the age of child’s literacy, maternal education level, out-migrant workers, and prolonged screen exposure during pregnancy. The home literacy environment accounted for most of the variance within both groups. Then we examined shared polygenic risks between DD, attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, major depressive disorder, and bipolar disorder using polygenic risk score (PRS) analyses. The results showed that the highest PRS DD quartile had a 2.13-fold risk than the lowest quartile with risk factors adjusted (95% CI: 1.08, 4.18). The individuals with the highest PRS ASD quartile and PRS SCZ quartile (OR: 2.13; 95% CI: 1.14, 3.98 and OR: 2.41; 95% CI: 1.23, 4.72) were associated with increasing dyslexia risks. This study identified the importance of screening personalized environmental factors among dyslexia and highlighted the shared genetic architecture between dyslexia and other disorders. These findings offered novel insight into the etiology of dyslexia, contributing to the advancement of early prevention strategies.