Talkowski Michael E, Seltman Howard, Bassett Anne S, Brzustowicz Linda M, Chen Xiangning, Chowdari Kodavali V, Collier David A, Cordeiro Quirino, Corvin Aiden P, Deshpande Smita N, Egan Michael F, Gill Michael, Kendler Kenneth S, Kirov George, Heston Leonard L, Levitt Pat, Lewis David A, Li Tao, Mirnics Karoly, Morris Derek W, Norton Nadine, O'Donovan Michael C, Owen Michael J, Richard Christian, Semwal Prachi, Sobell Janet L, St Clair David, Straub Richard E, Thelma B K, Vallada Homero, Weinberger Daniel R, Williams Nigel M, Wood Joel, Zhang Feng, Devlin Bernie, Nimgaonkar Vishwajit L
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Biol Psychiatry. 2006 Jul 15;60(2):152-62. doi: 10.1016/j.biopsych.2006.02.015. Epub 2006 Apr 21.
Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles.
In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807).
The family-based dataset consisted of 10 samples (2160 families). Significant associations with individual SNPs/haplotypes were not observed. In contrast, global analysis revealed significant transmission distortion (p = .0009). Specifically, analyses suggested overtransmission of two common haplotypes that account for the vast majority of all haplotypes. Separate analyses of 3486 cases and 3755 control samples (eight samples) detected a significant association with SNP 4 (p = .01). Individual haplotype analyses were not significant, but evaluation of test statistics from individual samples suggested significant associations.
Our collaborative meta-analysis represents one of the largest SCZ association studies to date. No individual risk factor arose from our analyses, but interpretation of these results is not straightforward. Our analyses suggest risk due to at least two common haplotypes in the presence of heterogeneity. Similar analysis for other putative susceptibility genes is warranted.
已有报道称精神分裂症（SCZ）与G蛋白信号调节因子4（RGS4）基因的多态性之间存在关联（单核苷酸多态性[SNPs]1、4、7和18）。然而，与其他SCZ候选基因类似，关于相关等位基因的研究结果并不一致。
为了明确RGS4在SCZ易感性中的作用，我们使用已发表和未发表的基于家系及病例对照的样本进行了一项基于基因型的荟萃分析（样本总数n = 13,807）。
基于家系的数据集包含10个样本（2160个家系）。未观察到与单个SNP/单倍型的显著关联。相比之下，整体分析显示出显著的传递不平衡（p = 0.0009）。具体而言，分析表明两种常见单倍型存在过度传递，这两种单倍型占所有单倍型的绝大多数。对3486例病例和3755例对照样本（8个样本）进行的单独分析检测到与SNP 4存在显著关联（p = 0.01）。单个单倍型分析无显著意义，但对各个样本检验统计量的评估表明存在显著关联。
我们的协作荟萃分析是迄今为止最大规模的SCZ关联研究之一。我们的分析未发现单一的风险因素，但这些结果的解释并不简单。我们的分析表明，在存在异质性的情况下，至少两种常见单倍型会导致风险。对其他假定的易感基因进行类似分析是有必要的。
