Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA, United States; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
Psychoneuroendocrinology. 2013 Oct;38(10):2249-57. doi: 10.1016/j.psyneuen.2013.04.013. Epub 2013 Jun 21.
The ankyrin 3 gene (ANK3) produces the ankyrin G protein that plays an integral role in regulating neuronal activity. Previous studies have linked ANK3 to bipolar disorder and schizophrenia. A recent mouse study suggests that ANK3 may regulate behavioral disinhibition and stress reactivity. This led us to hypothesize that ANK3 might also be associated with stress-related psychopathology such as posttraumatic stress disorder (PTSD), as well as disorders of the externalizing spectrum such as antisocial personality disorder and substance-related disorders that are etiologically linked to impulsivity and temperamental disinhibition.
We examined the possibility of association between ANK3 SNPs and both PTSD and externalizing (defined by a factor score representing a composite of adult antisociality and substance abuse) in a cohort of white non-Hispanic combat veterans and their intimate partners (n=554). Initially, we focused on rs9804190-a SNP previously reported to be associated with bipolar disorder, schizophrenia, and ankyrin G expression in brain. Then we examined 358 additional ANK3 SNPs utilizing a multiple-testing correction.
rs9804190 was associated with both externalizing and PTSD (p=0.028 and p=0.042 respectively). Analysis of other ANK3 SNPs identified several that were more strongly associated with either trait. The most significant association with externalizing was observed at rs1049862 (p=0.00040, pcorrected=0.60). The most significant association with PTSD (p=0.00060, pcorrected=0.045) was found with three SNPs in complete linkage disequilibrium (LD)-rs28932171, rs11599164, and rs17208576.
These findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia.
ankyrin 3 基因（ANK3）产生的锚蛋白 G 蛋白在调节神经元活动中起着重要作用。先前的研究将 ANK3 与双相情感障碍和精神分裂症联系在一起。最近的一项小鼠研究表明，ANK3 可能调节行为抑制和应激反应。这使我们假设 ANK3 也可能与创伤后应激障碍（PTSD）等与应激相关的精神病理学有关，以及反社会人格障碍和物质相关障碍等外化谱障碍，这些障碍与冲动和气质抑制有关。
我们在一个由白种非西班牙裔战斗退伍军人及其亲密伴侣（n=554）组成的队列中，研究了 ANK3 SNP 与 PTSD 和外化（由代表成年反社会行为和物质滥用的综合因素得分定义）之间的关联可能性。最初，我们专注于 rs9804190-一种先前报道与双相情感障碍、精神分裂症和大脑中锚蛋白 G 表达相关的 SNP。然后，我们利用多重测试校正检查了 358 个额外的 ANK3 SNP。
rs9804190 与外化和 PTSD 均相关（p=0.028 和 p=0.042）。对其他 ANK3 SNP 的分析确定了一些与这些特征相关性更强的 SNP。与外化最显著相关的是 rs1049862（p=0.00040，p 校正=0.60）。与 PTSD 最显著相关的是 rs28932171、rs11599164 和 rs17208576 三个 SNP 完全连锁不平衡（LD）时（p=0.00060，p 校正=0.045）。
这些发现支持 ANK3 在应激相关和外化障碍风险中的作用，超出了其先前与双相情感障碍和精神分裂症的关联。
