Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese
Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese
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涵盖 PDZ-GEF2、LOC728637 和 ACSL6 的单倍型与汉族精神分裂症的关联
DOI：
10.1136/jmg.2008.060657
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发表时间：
2008-12-01
影响因子：
4
通讯作者：
Su, B.
中科院分区：
文献类型：
--
作者：
Luo, X-j;Diao, H-b;Su, B.
背景：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性疾病。一些连锁和关联研究一再表明，染色体5q22 - 33区域与精神分裂症的病因有关。然而，大多数关于5q22 - 33与精神分裂症的联系的先前研究都来自欧洲人群，并且在其他人群中没有得到很好的表征。研究方法：我们分析了位于5q23.3区域的8个单核苷酸多态性（SNPs），在一个队列的506例精神分裂症患者和672名对照组来自中国西南地区。进行了单标记关联、单倍型关联、性别特异关联和分子进化分析。结果：单标记分析表明，LOC728637的SNP5（rs1355095）与精神分裂症相关。当分别分析男性和女性时，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、L0C728637和ACSL6的单倍型块与精神分裂症高度相关，并且该单倍块中的几种单倍型在受影响的受试者中增加约2倍至10倍。此外，分子进化分析表明，PDZ-GEF 2已经经历了适应性进化，由于达尔文主义的积极选择在人类谱系。结论：5q22 - 33与汉族精神分裂症有关联。这一染色体区域可能与精神分裂症的遗传易感性有关，支持了欧洲患者先前的数据。此外，我们的进化分析是一致的假设，即基因有助于精神分裂症可能在人类进化过程中的积极选择。
Background: 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. Methods: 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. Results: 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. Conclusion: 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.