Neuropsychiatric Genetics Research Group, Trinity College Dublin, Dublin, Ireland.
Neuroimage. 2011 Feb 1;54(3):2132-7. doi: 10.1016/j.neuroimage.2010.09.089. Epub 2010 Oct 8.
ZNF804A rs1344706 is the first genetic risk variant to achieve genome wide significance for psychosis. Following earlier evidence that patients carrying the ZNF804A risk allele had relatively spared memory function compared to patient non-carriers, we investigated whether ZNF804A was also associated with variation in brain volume. In a sample of 70 patients and 38 healthy participants we used voxel based morphometry to compare homozygous (AA) carriers of the ZNF804A risk allele to heterozygous and homozygous (AC/CC) non-carriers for both whole brain volume and specific regions implicated in earlier ZNF804A studies-the dorsolateral pre-frontal cortex, the hippocampus, and the amygdala. For patients, but not for controls, we found that homozygous 'AA' risk carriers had relatively larger gray matter volumes than heterozygous/homozygous non-carriers (AC/CC), particularly for hippocampal volumes. These data are consistent with our earlier behavioral data and suggest that ZNF804A is delineating a schizophrenia subtype characterized by relatively intact brain volume. Establishing if this represents a discrete molecular pathogenesis with consequences for nosology and treatment will be an important next step in understanding ZNF084A's role in illness risk.
ZNF804A rs1344706 是首个达到全基因组意义的精神分裂症遗传风险变异。在先前的证据表明,携带 ZNF804A 风险等位基因的患者与非携带者相比,记忆功能相对保留之后,我们研究了 ZNF804A 是否与脑容量的变化有关。在 70 名患者和 38 名健康参与者的样本中,我们使用基于体素的形态测量学,比较了 ZNF804A 风险等位基因纯合(AA)携带者与杂合子(AC/CC)和纯合子(AC/CC)非携带者的全脑体积以及与 ZNF804A 早期研究相关的特定区域(背外侧前额叶皮层、海马体和杏仁核)的体积。对于患者,但不是对照者,我们发现纯合“AA”风险携带者的灰质体积比杂合子/纯合子非携带者(AC/CC)相对较大,特别是海马体体积。这些数据与我们早期的行为数据一致,表明 ZNF804A 描绘了一种以相对完整的脑容量为特征的精神分裂症亚型。确定这是否代表一种具有分类学和治疗意义的离散分子发病机制,将是理解 ZNF084A 在疾病风险中的作用的重要下一步。