The cognitive and neural implications of computer gaming have garnered significant attention, yet the causal relationships remain unclear. This study investigates these relationships using Mendelian randomization (MR). Utilizing publicly available genome-wide association study data, we conducted a two-sample MR to assess the direct association between computer gaming and cognitive function, and a two-step MR to investigate the mediating role of brain cortical structure. The inverse-variance weighted analysis showed significant positive effects of computer gaming on visual memory [β = −0.552, 95% confidence interval (CI): −0.700 to −0.405, P = 1.98 × 10−13] and reaction time (β = −0.357, 95% CI: −0.444 to −0.271, P = 4.40 × 10−16). The mediation analysis identified the cortical surface area of the rostral anterior cingulate cortex as a significant mediator, explaining a mediated proportion of 6.88% (95% CI: 0.57% to 13.19%, P = 0.026). Sensitivity analyses confirmed the robustness of these findings. This study provides evidence for the causal impact of computer gaming on cognitive function, mediated by changes in brain cortical structure, suggesting potential for targeted cognitive training and rehabilitation interventions.
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