Luo X-j, Diao H-b, Wang J-k, Zhang H, Zhao Z-m, Su B
J Med Genet. 2008 Dec;45(12):818-26. doi: 10.1136/jmg.2008.060657. Epub 2008 Aug 21.
Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. Several lines of linkage and association studies have repeatedly suggested that the chromosome 5q22-33 region is implicated in the aetiology of schizophrenia. However, most of the previous studies on the linkage of 5q22-33 with schizophrenia were from European populations, and it was not well characterised in other populations.
We analysed eight single nucleotide polymorphisms (SNPs) located in the 5q23.3 region in a cohort of 506 schizophrenia patients and 672 control subjects from south western China. Single marker association, haplotypic association, sex-specific association and molecular evolutionary analysis were performed.
Single marker analysis indicated that SNP5 (rs1355095) in LOC728637 is associated with schizophrenia. When males and females were analysed separately, SNP4 (rs31251) in PDZ-GEF2 is associated with schizophrenia in females. Further analysis using haplotypes demonstrated that a haplotype block spanning PDZ-GEF2, LOC728637 and ACSL6 is highly associated with schizophrenia and several haplotypes in this haploblock have about twofold to 10-fold increase in the affected subjects. In addition, molecular evolutionary analysis suggests that PDZ-GEF2 has undergone adaptive evolution due to Darwinian positive selection in the human lineage.
Our data provide evidence of the association of 5q22-33 with schizophrenia in Han Chinese. This chromosomal region is likely responsible for genetic susceptibility to schizophrenia, supporting previous data from European patients. In addition, our evolutionary analysis is consistent with the hypothesis that genes contributing to schizophrenia are likely under positive selection during human evolution.
精神分裂症是一种由多种遗传和环境因素引起的复杂遗传疾病。多项连锁和关联研究反复表明，染色体5q22 - 33区域与精神分裂症的病因有关。然而，先前关于5q22 - 33与精神分裂症连锁的大多数研究来自欧洲人群，在其他人群中并未得到很好的表征。
我们分析了来自中国西南部的506例精神分裂症患者和672例对照受试者队列中位于5q23.3区域的8个单核苷酸多态性（SNP）。进行了单标记关联、单倍型关联、性别特异性关联和分子进化分析。
单标记分析表明，LOC728637中的SNP5（rs1355095）与精神分裂症相关。当分别对男性和女性进行分析时，PDZ - GEF2中的SNP4（rs31251）与女性精神分裂症相关。使用单倍型的进一步分析表明，跨越PDZ - GEF2、LOC728637和ACSL6的一个单倍型块与精神分裂症高度相关，并且该单倍型块中的几个单倍型在患病受试者中增加了约两倍至10倍。此外，分子进化分析表明，由于人类谱系中的达尔文正选择，PDZ - GEF2经历了适应性进化。
我们的数据提供了5q22 - 33与汉族人群精神分裂症关联的证据。该染色体区域可能是精神分裂症遗传易感性的原因，支持了先前来自欧洲患者的数据。此外，我们的进化分析与以下假设一致，即在人类进化过程中，导致精神分裂症的基因可能处于正选择之下。
