Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil
Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil
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DOI：
10.1111/j.1601-183x.2004.00096.x
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发表时间：
2005-02-01
影响因子：
2.5
通讯作者：
Vallada, H
中科院分区：
文献类型：
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作者：
Cordeiro, Q;Talkowski, ME;Vallada, H
在五个独立确定的样本中的连锁和关联研究表明，G蛋白信号转导调节因子4(RGS4)的多态性可能增加精神分裂症(SCZ)的风险。还提出了与双相情感障碍(BD)相关的提示性证据。然而，相关的等位基因和单倍型在样本之间是不同的。来自其他独立样本的数据可能会澄清推定的联系。因此，我们调查了一个独立的、种族多样化的巴西人，其中包括SCZ患者(n=271)或BD1患者(n=306)，他们与576名基于社区的对照组进行了对比。49例SCZ和44例BD的父母可用于传递不平衡检验(TDT)。研究了4个可能与SCZ相关的RGS4单核苷酸多态(SNPs)1、4、7和18。在SCZ样本中，没有观察到单个SNPs或单倍型的显著病例对照差异，尽管TDT表明传递扭曲与最初报告中观察到的类似。对于BD样本，病例对照比较显示单个SNPs没有显著差异，但综合检验表明携带所有四个SNPs的单倍型总体分布存在差异(SNP-EM综合似然比检验；P=0.003)。TDT检测发现A等位基因在SNP7位点过度传递(P=0.016)，并存在含有该等位基因的单倍型。然而，包括所有单倍型的全球测试只产生了关联的提示趋势(P=0.19)。总而言之，在目前的分析中没有检测到与SCZ有关。未能发现关联可能与权力不足或与种族混杂有关的混乱有关。在这里检测到的与BD的暗示关联需要在更大的样本中进行进一步的调查。
Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G-protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n=271) or BD1 (n=306), who were contrasted with 576 community-based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). Four RGS4 single-nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case-control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case-control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP-EM Omnibus likelihood ratio test; P=0.003). The TDT revealed over-transmission of allele A at SNP7 (P=0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P=0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample.