Abstract:

BACKGROUND: Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals.
METHODS: In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains.
RESULTS: Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals.
LIMITATIONS: The sample size of patients with bipolar disorder was small, and most of the patients were on psychotropic medication.
CONCLUSIONS: These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder.

日本語要旨:

本研究では、ゲノムワイド関連解析において双極性障害と関連することが示されたANK3の一塩基多型rs10994336とrs10761482が、双極性障害の中間表現型である認知機能にどのような影響を与えているのかを調べた。Rs10761482のリスクアレルを保有している双極性障害患者では、保有していない患者に比べ、言語理解、論理的記憶、処理速度の成績が有意に低く、リスクアレルを保有している健常者では、保有していない健常者に比べ、実行機能と視覚性記憶の成績が有意に低いという結果が得られた。これらの結果は、ANK3のリスク多型は認知機能に影響を与えることで双極性障害と関連するという可能性を示唆する。