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

Psychiatry Clin Neurosci. 2016 Nov;70(11):498-506. doi: 10.1111/pcn.12431. Epub 2016 Sep 29.

Abstract

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.

Keywords: ankyrin 3; bipolar disorder; diffusion tensor imaging; tract-based spatial statistics; voxel-based morphometry.

MeSH terms

  • Adult
  • Ankyrins / genetics*
  • Bipolar Disorder / diagnostic imaging*
  • Bipolar Disorder / genetics*
  • Brain / diagnostic imaging*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk

Substances

  • ANK3 protein, human
  • Ankyrins