Neuropsychiatric Genetics Group, Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin, Ireland.
Genes Brain Behav. 2013 Mar;12(2):203-9. doi: 10.1111/gbb.12016.
The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, was recently identified as genome-wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non-carriers of the risk 'A' allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients (n = 387) and controls (n = 171) and German patients (205) and controls (n = 533). Across these groups, the risk 'A' allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified 'A' risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk.
单核苷酸多态性（SNP）rs10503253 位于 8p23.2 上的 CUB 和 Sushi 多结构域-1（CSMD1）基因内，最近被确定为与精神分裂症（SZ）全基因组显著相关，但功能未知。我们使用脑结构和功能的行为和成像测量，在体内研究了该 CSMD1 变体在患者和健康参与者中的神经认知效应。我们在独立的爱尔兰患者（n = 387）和对照组（n = 171）和德国患者（205）和对照组（n = 533）样本中，比较了风险 'A' 等位基因携带者和非携带者在 SZ 中通常受损的神经心理表现（一般认知能力、情景和工作记忆以及注意力控制）的神经认知性能的测量值。在这些组中，CSMD1 的风险 'A' 等位基因与多种神经认知表型的有害影响有关。具体来说，风险等位基因与神经心理学一般认知能力和记忆功能的测量值较差有关，但与注意力控制无关。这些影响虽然显著，但很细微，并且在样本之间存在差异。与先前的证据一致，表明 CSMD1 可能参与与记忆和学习相关的大脑机制，这些数据似乎反映了已识别的 'A' 风险等位基因对神经认知功能的有害影响，可能是 CSMD1 与 SZ 风险相关的机制的一部分。
