本文選題：精神分裂癥　切入點：雙相情感障礙　出處：《上海交通大學(xué)》2012年博士論文　論文類型：學(xué)位論文

【摘要】：精神分裂癥（Schizophrenia），重度抑郁癥（Major Depression Disorder）和雙向情感障礙（Bipolar Disorder）是三種常見的精神疾病。精神分裂癥是非常嚴(yán)重的一類精神疾病，發(fā)病率大約為1%。在北美人群中，重度抑郁癥在男性中的患病率大約為3 5%，在女性中的患病率大約為8 10%，并且該病也被認(rèn)為是與遺傳因素相關(guān)的。雙相情感障礙也是一種嚴(yán)重的的精神疾病，在美國成人中的發(fā)病率大約為2.2%。雖然以上這些疾病的的發(fā)病原因我們還并不清楚，遺傳因素在各種疾病的發(fā)病原因中都是重要的一部分。 近期，一項全基因組關(guān)聯(lián)研究及后續(xù)驗證的工作取得了重要進(jìn)展。該研究由Stefansson等人開展，研究所涉及的樣本包含7676個精神分裂癥病例和29057個正常對照，這個個體都來自高加索人群。他們發(fā)現(xiàn)了7個常見的單核苷酸多態(tài)性位點與精神分裂癥顯著相關(guān)。為了研究這些風(fēng)險位點在漢族人群中是否也與精神分裂癥顯著相關(guān)，我們在2496例精神分裂癥患者和5184例正常對照中開展了這項研究，這也是這篇論文的第一部分。我們發(fā)現(xiàn)，在上述7個位點中，有4個只有一種基因型。因此，我們在風(fēng)險區(qū)域又額外選了2個位點來分析。最后，我們發(fā)現(xiàn)，在人主要組織相容性復(fù)合體基因區(qū)域的rs6932590(p=0.00096),rs3131296(p=1.29×10~(-6))和rs3130375(p=1.76×10~(-5))，還有位于TCF4基因內(nèi)的rs2958182(p=3.64×10~(-6))在漢族人群中與精神分裂癥是顯著相關(guān)的。我們也綜合國外的全基因組關(guān)聯(lián)研究的結(jié)果進(jìn)行了薈萃分析。我們的結(jié)果支持了MHC區(qū)域和TCF4基因在漢族人群中與精神分裂癥顯著相關(guān)，但是我們并沒有得到NRGN基因與該疾病關(guān)聯(lián)的結(jié)論。 在論文的第二部分，我們關(guān)注了FoxP2基因，該基因定位在7q31上，編碼一個轉(zhuǎn)錄因子。該基因最先在一個多代的語言障礙的家系（the KE family）中被發(fā)現(xiàn)。后續(xù)的研究給出了非常具有說服力的證據(jù)，證明FoxP2基因和語言障礙之間是有聯(lián)系的。言語失常被認(rèn)為是精神分裂癥及其他一些精神疾病的核心特征之一，因此，我們想研究該基因在精神分裂癥、重度抑郁癥、雙相情感障礙的發(fā)病重是否起著重要的作用。在這項研究中，我們分析了基因內(nèi)的12個SNPs位點并且在1135例精神分裂癥患者，1135例雙相情感障礙患者，1135例重度抑郁癥，1135例正常對照中進(jìn)行了病例—對照研究。我們發(fā)現(xiàn)rs10447760與精神分裂癥（等位基因的P值為0.00069）和重度抑郁癥（等位基因的P值為0.0011）顯著相關(guān)。我們的研究說明該位點可能在漢族人的精神分裂癥、重度抑郁癥的發(fā)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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R749

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