The Association of RAB18 Gene Polymorphism (rs3765133) with Cerebellar Volume in Healthy Adults

Genetic factors are responsible for the development of the human brain. Certain genetic factors are known to increase the risk of common brain disorders and affect the brain structure. Therefore, even in healthy people, these factors have a role in the development of specific brain regions. Loss-of-function mutations in the RAB18 gene (RAB18) cause Warburg Micro syndrome, which is associated with reduced brain size and deformed brain structures. In this study, we hypothesized that the RAB18 variant might influence regional brain volumes in healthy people. The study participants comprised 246 normal volunteers between 21 and 59 years of age (mean age of 37.8 ± 12.0 years; 115 men, 131 women). Magnetic resonance imaging (MRI) and genotypes of RAB18 rs3765133 were examined for each participant. The differences in regional brain volumes between T homozygotes and A-allele carriers were tested using voxel-based morphometry. The results showed that RAB18 rs3765133 T homozygote group exhibited larger gray matter (GM) volume in the left middle temporal and inferior frontal gyrus of the cerebrum than the A-allele carriers. An opposite effect was observed in both the posterior lobes and right tonsil of the cerebellum, in which the GM volume of RAB18 rs3765133 T homozygotes was smaller than that of the A-allele carriers (all P_FWE < 0.05). Our findings suggest that RAB18 rs3765133 polymorphism affects the deve-lopment of specific brain regions, particularly the cerebellum, in healthy people.