Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.
Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.
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DOI：
10.1371/journal.pone.0070302
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yoshikawa T
中科院分区：
文献类型：
--
作者：
Balan S;Yamada K;Hattori E;Iwayama Y;Toyota T;Ohnishi T;Maekawa M;Toyoshima M;Iwata Y;Suzuki K;Kikuchi M;Yoshikawa T
突触后密度（PSD）的突触能突触窝藏大量的蛋白质，维持突触动力学的关键。该基质中蛋白质表达水平的改变是神经精神疾病包括精神分裂症的显著现象，其中认知功能受损。为了研究PSD中表达的基因与精神分裂症的遗传关系，使用日本样本（124个家系，n = 376名受试者）对PSD基因中的遗传变异（如DLG 4，DLG 1，PICK 1和MDM 2）进行了基于家族的关联分析。 结果显示，DLG 4基因的rs 17203281变异与C等位基因的优先传递显著相关（p = 0.02），尽管多重检验校正后显著性消失。 对该变异的重复分析发现，在中国精神分裂症队列（293个家系，n = 1163例受试者）或日本病例对照样本（n = 4182例受试者）中没有相关性。 精神分裂症患者死后脑组织样本中DLG 4的表达水平与对照组相比没有显著变化。有趣的是，DLG 4中的五个标记单倍型，包括rs 2242449、rs 17203281、rs390200、rs 222853和rs 222837，以群体特异性方式富集，其中序列A-C-C-C-A和G-C-C-C-A分别在日本（p = 0.0009）和中国（p = 0.0007）精神分裂症家系样品中积累。 然而，这在病例对照样本中无法复制。在这些样本中，其他检查的候选基因中没有任何变异显示出任何显著的关联。目前的研究强调了DLG 4在精神分裂症发病机制中的假定作用，证明了单倍型关联，并保证进一步密集筛选这些单倍型中的变体。
The post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects) or in a Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007) schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes.
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影响因子：
1.7
作者：
Hong, CJ;Liao, DL;Tsai, SJ
通讯作者：
Tsai, SJ
影响因子：
3.7
作者：
Catts VS;Weickert CS
通讯作者：
Weickert CS
影响因子：
5.3
作者：
Klei, L;Bacanu, SA;Byerley, W
通讯作者：
Byerley, W
影响因子：
11
作者：
Bergen, S. E.;O'Dushlaine, C. T.;Ripke, S.;Lee, P. H.;Ruderfer, D. M.;Akterin, S.;Moran, J. L.;Chambert, K. D.;Handsaker, R. E.;Backlund, L.;Osby, U.;McCarroll, S.;Landen, M.;Scolnick, E. M.;Magnusson, P. K. E.;Lichtenstein, P.;Hultman, C. M.;Purcell, S. M.;Sklar, P.;Sullivan, P. F.
通讯作者：
Sullivan, P. F.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y