A genetic association study of CSMD1 and CSMD2 with cognitive function
A genetic association study of CSMD1 and CSMD2 with cognitive function
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DOI：
10.1016/j.bbi.2016.11.026
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发表时间：
2017-03-01
影响因子：
15.1
通讯作者：
Le Hellard, Stephanie
中科院分区：
文献类型：
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作者：
Athanasiu, Lavinia;Giddaluru, Sudheer;Le Hellard, Stephanie
补体级联在突触修剪和突触可塑性中发挥作用，这似乎与认知功能和精神障碍有关。与补体调节密切相关的CSMD1和CSMD2基因的遗传变异与精神分裂症有关。由于精神分裂症患者经常表现出认知障碍，我们测试了CSMD1和CSMD2的变异是否也与认知功能本身有关。我们采取了发现-复制的方法，使用了特征良好的斯堪的纳维亚队列。在NCNG样本中，共测试了CSMD1中的1637个SNPs和CSMD2中的206个SNPs与认知功能的关联(挪威认知神经遗传学；n=670)。对p值为0.001的SNP(CSMD1中7个，CSMD2中3个)的复制测试在顶部样本(按主题组织的精神病；n=1025)和Betula样本(关于衰老、记忆和痴呆的Betula纵向研究；n=1742)中进行。最后，我们使用所有三个样本对这些SNPs进行了Meta分析。CSMD1(SNP Rs10503253)中先前发现的精神分裂症标记物也包括在内。CSMDI SNP rs2740931与即刻情景记忆成绩的相关性最强(p值=5CH10(-6)，次要等位基因A，MAF 0.48~0.49，负效应方向)。这种联系达到了整个研究的显著水平(p
The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p