Association Analysis of Schizophrenia on 18 Genes Involved in Neuronal Migration: MDGA1 as a New Susceptibility Gene
Association Analysis of Schizophrenia on 18 Genes Involved in Neuronal Migration: MDGA1 as a New Susceptibility Gene
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DOI：
10.1002/ajmg.b.30726
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发表时间：
2008-10-05
影响因子：
2.8
通讯作者：
Andreassen, Ole A.
中科院分区：
文献类型：
--
作者：
Kahler, Anna K.;Djurovic, Srdjan;Andreassen, Ole A.
有几条证据支持精神分裂症（SZ）是一种神经发育障碍的理论。在SZ患者中报告的结构、细胞结构和功能性脑异常可能是由于异常神经元迁移，因为神经元的最终位置影响神经元功能、形态和突触连接的形成。我们通过对839例斯堪的纳维亚起源的病例和1,473例对照进行关联研究，调查了SZ和参与神经元迁移过程的基因变异之间的假定关联。使用全基因的方法，在18个候选基因的tagSNPs基因分型，与神经元到神经胶质细胞粘附，与DISCI的相互作用的基因产物。蛋白质和/或细胞骨架的重排。在所测试的289个标记中，位于基因MDGA 1、MDGA N、ITGA 3、DLX 1、SPARCL 1和ASTN 1中的19个标记在基因型或等位基因关联检验中获得名义上显著的P值（P < 0.05）。除转录因子DLX 1外，所有这些基因均参与神经元与放射状胶质细胞之间的粘附。8个标记在两个测试中获得名义上的显著性，并且位于粘附分子MDGA 1和先前报道的SZ候选人ADN的内含子或3 'UTR区域。MDGA 1 SNP rs 9462341获得了最显著的结果（未校正的关联结果：基因型P = 0.00095;等位基因P = 0.010）。MDGA 1、ITGA 3和ENAH中的几种单倍型名义上是显著的。需要在独立样本中进行进一步研究，包括即将到来的全基因组关联研究结果，但我们的数据表明MDGA 1是一个新的SZ易感基因，并且改变的神经元迁移参与SZ病理学。(C)2008 Wiley-Liss，Inc.
Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISCI. protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P < 0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology. (C) 2008 Wiley-Liss, Inc.