Effects of ankyrin 3 gene risk variants on brain structures in patients with bipolar disorder and healthy subjects

Aim: The intronic single-nucleotide polymorphism rs10994336 of the ankyrin 3 gene (ANK3) is one of the genome-wide supported risk variants for bipolar disorder (BD), and the T-allele of rs10761482 is also reported to have relevance to BD. We investigated the effect of ANK3 rs10761482 genetic variation on brain structure. Methods: Subjects were 43 BD patients and 229 healthy volunteers. We evaluated the effects of ANK3 rs10761482 genetic variation on diagnosis, and of the genotype-by-diagnosis interaction on the brain structure and the degree of age-related brain atrophy on magnetic resonance imaging data evaluated by voxel-based morphometry. Results: BD patients showed significantly lower fractional anisotropy value in the bilateral parietal regions, left fronto-occipital fasciculus, and corpus callosum, compared to healthy subjects. Further, we found considerable decreases of fractional anisotropy in the forceps minor in non-T-allele BD patients compared with the T-carrier patient group. We also found significant lessening of age-related brain atrophy in the T-allele carrier groups compared with the non-T-allele carrier groups in the area around the cerebrospinal space, cingulate cortices, and cerebellum. Conclusion: Our results suggest the influence of the ANK3 on age-related brain atrophy. The ankyrin 3 genotype may be associated with pathogenesis of age-related neurodegeneration, and, in part, of BD.