RAB2A Polymorphism impacts prefrontal morphology, functional connectivity, and working memory.

Calbindin-containing γ-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome-wide association and expression-SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin-positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI and behavioral tasks, the current study investigated the effect of RAB2A on prefrontal morphology, resting-state functional connectivity, and WM performance in a large sample of healthy Han Chinese subjects. Results showed that the RAB2A AGCAAA haplotype was associated with improved WM accuracy, increased cortical thickness in the left inferior frontal gyrus, and decreased functional connectivity between the left inferior frontal gyrus and the left dorsolateral PFC. Our findings provide consistent evidence supporting the effect of RAB2A on the structure and function of the PFC and related cognitive functions. These results should provide new insights into the neural mechanisms underlying the GABAergic genes' role in WM as well as its dysfunction.