基于大样本的精神疾病遗传易感性研究

发布时间：2018-03-04 09:38

本文选题：精神分裂症　切入点：双相情感障碍　出处：《上海交通大学》2012年博士论文　论文类型：学位论文

【摘要】：精神分裂症（Schizophrenia），重度抑郁症（Major Depression Disorder）和双向情感障碍（Bipolar Disorder）是三种常见的精神疾病。精神分裂症是非常严重的一类精神疾病，发病率大约为1%。在北美人群中，重度抑郁症在男性中的患病率大约为3 5%，在女性中的患病率大约为8 10%，并且该病也被认为是与遗传因素相关的。双相情感障碍也是一种严重的的精神疾病，在美国成人中的发病率大约为2.2%。虽然以上这些疾病的的发病原因我们还并不清楚，遗传因素在各种疾病的发病原因中都是重要的一部分。近期，一项全基因组关联研究及后续验证的工作取得了重要进展。该研究由Stefansson等人开展，研究所涉及的样本包含7676个精神分裂症病例和29057个正常对照，这个个体都来自高加索人群。他们发现了7个常见的单核苷酸多态性位点与精神分裂症显著相关。为了研究这些风险位点在汉族人群中是否也与精神分裂症显著相关，我们在2496例精神分裂症患者和5184例正常对照中开展了这项研究，这也是这篇论文的第一部分。我们发现，在上述7个位点中，有4个只有一种基因型。因此，我们在风险区域又额外选了2个位点来分析。最后，我们发现，在人主要组织相容性复合体基因区域的rs6932590(p=0.00096),rs3131296(p=1.29×10~(-6))和rs3130375(p=1.76×10~(-5))，还有位于TCF4基因内的rs2958182(p=3.64×10~(-6))在汉族人群中与精神分裂症是显著相关的。我们也综合国外的全基因组关联研究的结果进行了荟萃分析。我们的结果支持了MHC区域和TCF4基因在汉族人群中与精神分裂症显著相关，但是我们并没有得到NRGN基因与该疾病关联的结论。在论文的第二部分，我们关注了FoxP2基因，该基因定位在7q31上，编码一个转录因子。该基因最先在一个多代的语言障碍的家系（the KE family）中被发现。后续的研究给出了非常具有说服力的证据，证明FoxP2基因和语言障碍之间是有联系的。言语失常被认为是精神分裂症及其他一些精神疾病的核心特征之一，因此，我们想研究该基因在精神分裂症、重度抑郁症、双相情感障碍的发病重是否起着重要的作用。在这项研究中，我们分析了基因内的12个SNPs位点并且在1135例精神分裂症患者，1135例双相情感障碍患者，1135例重度抑郁症，1135例正常对照中进行了病例—对照研究。我们发现rs10447760与精神分裂症（等位基因的P值为0.00069）和重度抑郁症（等位基因的P值为0.0011）显著相关。我们的研究说明该位点可能在汉族人的精神分裂症、重度抑郁症的发病中起到重要作用。
[Abstract]:Schizophrenia, Major Depression Disorderand Bipolar Disorderare three common mental disorders. Schizophrenia is a very serious class of mental illness, with an incidence of about 1. The prevalence of severe depression is about 3 / 5 in men and 8 / 10 in women, and it is also thought to be genetic. Bipolar disorder is also a serious mental disorder. The incidence rate among adults in the United States is about 2.2 percent. Although the causes of these diseases are not yet clear, genetic factors are an important part of the causes of various diseases. Significant progress has recently been made in a genome-wide association study and subsequent validation by Stefansson et al., which involved 7676 schizophrenia cases and 29,057 normal controls. The individuals were from Caucasians. They found seven common single nucleotide polymorphisms associated with schizophrenia. In order to study whether these risk sites were also significantly associated with schizophrenia in the Han population, We conducted this study in 2,496 schizophrenic patients and 5184 normal controls, which was the first part of the study. We found that four of the seven loci had only one genotype. We selected two additional loci in the risk area to analyze. Finally, we found, Rs6932590, rs6932590, rs3131296, rs3131296, rs3131296, rs3131296, rs3131296p1. 29 脳 10 ~ (9), rs3130375(p=1.76 脳 10 ~ (10) -5, and rs2958182(p=3.64 脳 10 ~ (10) ~ (6), which are located in the TCF4 gene, are significantly associated with schizophrenia in the Han population. We have also combined the results of foreign genome-wide association studies. Our results suggest that the MHC region and the TCF4 gene are significantly associated with schizophrenia in the Han population. But we have not come to the conclusion that the NRGN gene is associated with the disease. In the second part of the paper, we focus on the FoxP2 gene, which is located on 7q31. Encoding a transcription factor. The gene was first found in the Ke family, a family with multigenerational language disorders. Speech disorders are thought to be one of the core features of schizophrenia and other mental disorders, so we want to study the gene in schizophrenia, severe depression, Whether the weight of bipolar disorder plays an important role. In this study, We analyzed 12 SNPs loci in the gene and conducted a case-control study in 1135 patients with bipolar affective disorder, 1135 patients with severe depression and 1135 normal controls. We found rs10447760 and psychiatric scores. There was a significant correlation between schizophrenia (P = 0.00069) and severe depression (P = 0.0011). The pathogenesis of severe depression plays an important role.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749

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