精神分裂癥候選基因、臨床癥狀及認(rèn)知功能的相關(guān)性研究
發(fā)布時(shí)間：2018-07-26 19:54
【摘要】：精神分裂癥是最常見、最嚴(yán)重的精神性疾病，多發(fā)于青壯年，世界人口中患病率約為1%；主要表現(xiàn)為精神活動(dòng)與現(xiàn)實(shí)環(huán)境想脫離、認(rèn)知、情感、意志及個(gè)性特征等各個(gè)方面不協(xié)調(diào)、相互分裂的疾病。精神分裂癥發(fā)病主要受環(huán)境和遺傳兩大因素影響。家系、雙生子及寄養(yǎng)子研究結(jié)果均表明遺傳因素在其發(fā)病中具有重要作用。精神分裂癥基因組掃描和候選基因研究，雖獲得不少陽性結(jié)果，但重復(fù)性較差，結(jié)果爭(zhēng)議很大。精神分裂癥臨床癥狀和認(rèn)知功能受諸多因素影響，其遺傳因素將會(huì)備受關(guān)注。 目的 利用生物信息學(xué)、分子遺傳學(xué)技術(shù)及生物統(tǒng)計(jì)學(xué)方法，一方面探討DBH、ACE、COMT、DRD2、CHRNA5、IL-10、IL-18、COX-2、TCF4、CACNA1C、MTHFR及GNB1L候選基因上SNPs與精神分裂癥關(guān)聯(lián)性，另一方面檢驗(yàn)這些SNPs是否影響受試者臨床癥狀和認(rèn)知功能，試圖揭示精神分裂癥易感基因及影響臨床癥狀和認(rèn)知功能的遺傳機(jī)制。 方法 本研究以350例首發(fā)精神分裂癥，567例慢性精神分裂癥和421例健康對(duì)照為研究對(duì)象。精神分裂癥患者來自北京回龍觀醫(yī)院住院部，正常健康人群來自當(dāng)?shù)厣鐓^(qū)。所有研究對(duì)象均為中國漢族人，并且精神分裂癥患者要符合ICD-10和CCMD-II-R的診斷標(biāo)準(zhǔn)。 在征得受試者知情同意的情況下，采集外周靜脈血，采用Promega (USA)液體純化提取DNA試劑盒，提取基因組DNA。利用PCR-AFLP和SequenomMassArray技術(shù)，檢測(cè)12個(gè)候選基因13個(gè)SNPs位點(diǎn)（rs141116007、rs4340、rs4680、rs1800497、rs3829787、rs1800872、rs1946518、rs689466、rs5275、rs2958182、rs2239050、rs1801133和rs748806）。 應(yīng)用在線遺傳統(tǒng)計(jì)SHEsis軟件計(jì)算基因型頻率分布是否符合Hardy-Weinberg平衡定律；分析候選基因SNPs位點(diǎn)與精神分裂癥的關(guān)聯(lián)性；分析基因各個(gè)位點(diǎn)之間連鎖不平衡程度及單倍型；應(yīng)用MDR軟件分析基因-基因間的交互作用；應(yīng)用SPSS17.0軟件分析候選基因SNPs位點(diǎn)與精神分裂癥臨床癥狀和認(rèn)知功能的相關(guān)性。結(jié)果 1, H-W平衡檢驗(yàn)和連鎖不平衡程度分析 （1）H-W平衡檢驗(yàn) rs4340、rs3829787和rs5275位點(diǎn)的基因型分布在首發(fā)精神分裂癥組中偏離H-W平衡；rs1800497、rs3829787和rs1801133位點(diǎn)的基因型分布在慢性精神分裂癥組中偏離H-W平衡；說明這些位點(diǎn)可能是疾病易感SNPs位點(diǎn)或與易感SNPs連鎖；其他位點(diǎn)基因型分布在首發(fā)精神分裂癥組、慢性精神分裂癥組和健康對(duì)照組中均符合H-W平衡定律（all, P＞0.05），說明本研究抽樣樣本符合遺傳學(xué)分析。 （2）連鎖不平衡程度分析 rs689466和rs5275處于高度連鎖不平衡染色體區(qū)，說明其位于連鎖不平衡區(qū)域內(nèi)。 2，病例-對(duì)照分析 (1)首發(fā)精神分裂癥-正常對(duì)照組單個(gè)SNP分析 rs141116007和rs5275位點(diǎn)與精神分裂癥發(fā)病相關(guān)聯(lián)，其等位基因和基因型頻率分布在病例組和對(duì)照組中均出現(xiàn)顯著性差異（all, P0.05）。rs2239050和rs3829787位點(diǎn)可能與精神分裂癥發(fā)病相關(guān)聯(lián)。rs2239050等位基因和rs3829787基因型的頻率分布在病例組和對(duì)照組中出現(xiàn)顯著差異（both, P0.05）。 (2)慢性精神分裂癥-正常對(duì)照組單個(gè)SNP分析 rs4340、rs1801133和rs748806位點(diǎn)與精神分裂癥發(fā)病相關(guān)聯(lián)，其等位基因和基因型頻率分布在兩組中均出現(xiàn)顯著性差異（all, P0.05）。rs1800497位點(diǎn)可能與精神分裂癥發(fā)病相關(guān)聯(lián)，其基因型頻率分布在病例組和對(duì)照組中出現(xiàn)顯著差異（P0.05）。 (3)病例對(duì)照組單倍型分析 對(duì)COX-2基因的2個(gè)SNPs位點(diǎn)進(jìn)行聯(lián)合分析。結(jié)果顯示，僅rs689466(C)-rs5275(A)作為保護(hù)型單倍型與首發(fā)精神分裂癥相關(guān)聯(lián)（P0.05）。 3，SNPs與精神分裂癥臨床癥狀的相關(guān)分析 (1) SNPs與首發(fā)精神分裂癥臨床癥狀的相關(guān)分析 在首發(fā)精神分裂癥中，DBH基因rs141116007位點(diǎn)和IL18基因rs1946518位點(diǎn)與首發(fā)精神分裂癥陽性癥狀和臨床癥狀總分相關(guān)（all, P0.05）；ACE基因rs4340位點(diǎn)與首發(fā)精神分裂癥陰性癥狀相關(guān)（P0.05）。 (2) SNPs與慢性精神分裂癥臨床癥狀的相關(guān)分析 在慢性精神分裂癥中，COX-2基因rs689466和rs5275位點(diǎn)與慢性精神分裂癥的陽性癥狀相關(guān)（both, P0.05）；TCF4基因rs2958182位點(diǎn)與慢性精神分裂癥陰性癥狀相關(guān)（P0.05）；IL-18基因rs1946518位點(diǎn)與慢性精神分裂癥臨床癥狀總分相關(guān)（P0.05）。 4，SNPs與認(rèn)知功能的相關(guān)分析 (1) SNPs與正常健康人認(rèn)知功能的相關(guān)分析 在正常健康對(duì)照中，TCF4基因rs2958182和CACNA1C基因rs2239050位點(diǎn)與正常健康人認(rèn)知功能的注意相關(guān)（both, P0.05）；COX-2基因rs5275位點(diǎn)與正常健康人認(rèn)知功能的語言相關(guān)（P0.05）；TCF4基因rs2958182位點(diǎn)與正常健康人認(rèn)知功能的延遲記憶和總分值相關(guān)（both, P0.05）。 (2) SNPs與首發(fā)精神分裂癥認(rèn)知功能的相關(guān)分析 在首發(fā)精神分裂癥中，DBH基因rs141116007、DRD2基因rs1800497位點(diǎn)和COX-2基因rs5275位點(diǎn)與首發(fā)精神分裂癥認(rèn)知功能的即刻記憶相關(guān)（all,P0.05）；COX-2基因rs689466位點(diǎn)和rs5275位點(diǎn)與首發(fā)精神分裂癥認(rèn)知功能的語言相關(guān)（all, P0.05）。 (3) SNPs與慢性精神分裂癥認(rèn)知功能的相關(guān)分析 在慢性精神分裂癥中，MTHFR基因rs18001133位點(diǎn)和IL-10基因rs1800872位點(diǎn)與慢性精神分裂癥注意能力相關(guān)（both, P0.05）；TCF4基因rs2958182位點(diǎn)和MTHFR基因rs18001133位點(diǎn)與慢性精神分裂癥的語言能力相關(guān)（both,P0.05）；DRD2基因rs1800497位點(diǎn)和TCF4基因rs2958182位點(diǎn)與慢性精神分裂癥認(rèn)知功能的延遲記憶相關(guān)（both, P0.05）；TCF4基因rs2958182位點(diǎn)與慢性精神分裂癥認(rèn)知功能的總分值相關(guān)（P0.05）。 結(jié)論 從上述分析可得到如下結(jié)論：(1) DBH、COX-2、CHRNA5和CACAN1C基因可能是首發(fā)精神分裂癥的易感基因；（2）ACE、DRD2、MTHFR和GNB1L基因可能是慢性精神分裂癥的易感基因；(3)首發(fā)精神分裂癥中DBH、IL-18基因和慢性精神分裂癥中COX-2基因分別與陽性癥狀相關(guān)（；4）首發(fā)精神分裂癥中ACE基因和慢性精神分裂癥中TCF4基因分別與陰性癥狀相關(guān)；（5）首發(fā)精神分裂癥中DBH、IL-18基因和慢性精神分裂癥中IL-18基因分別與臨床癥狀總分相關(guān)；（6）TCF4、CACNA1C和COX-2基因與正常健康人群認(rèn)知功能功能相關(guān)；（7）DBH、DRD2和COX-2基因與首發(fā)精神分裂癥認(rèn)知功能相關(guān)（；8）MTHFR、IL-10、DRD2、TCF4基因與慢性精神分裂癥認(rèn)知功能相關(guān)。（9）精神分裂癥存在遺傳和臨床的異質(zhì)性。
[Abstract]:Schizophrenia is the most common and most serious mental disease, mostly in young and young adults. The prevalence rate of the world population is about 1%. The main manifestations are the disharmony between mental activity and the realistic environment, the disharmony of cognition, emotion, will and personality. The main causes of schizophrenia are two major causes of environment and heredity. The results of the study of the family, the twins and the mailing seed all showed that the genetic factors played an important role in the disease. The genome scan and candidate gene study of schizophrenia have obtained a lot of positive results, but the reproducibility is poor and the result is very controversial. The clinical symptoms and cognitive functions of schizophrenia are affected by many factors, and their genetic causes are affected. It's going to get a lot of attention.
objective
Using bioinformatics, molecular genetics and biometric methods, the association of DBH, ACE, COMT, DRD2, CHRNA5, IL-10, IL-18, COX-2, TCF4, CACNA1C, MTHFR and GNB1L candidate genes to schizophrenia, on the other hand, to examine whether these effects affect the clinical symptoms and cognitive functions of the subjects and try to reveal the mental points. Susceptibility genes and genetic mechanisms affecting clinical symptoms and cognitive functions.
Method
In this study, 350 cases of first onset schizophrenia, 567 chronic schizophrenia and 421 healthy controls were studied. Schizophrenic patients came from the hospitalized Department of Beijing Hui Long Guan Hospital, and the normal healthy population came from the local community. All the subjects were Chinese Han people, and the patients with seminal schizophrenia had to meet the ICD-10 and CCMD-II-R diagnosis. Break the standard.
In the case of informed consent of the subjects, the peripheral venous blood was collected and the DNA kit was extracted with Promega (USA) liquid, and the genomic DNA. was extracted by PCR-AFLP and SequenomMassArray technology to detect the 13 SNPs loci of the 12 candidate genes (rs141116007, rs4340, rs4680, rs1800497, rs3829787. 958182, rs2239050, rs1801133 and rs748806).
The application of online genetic statistical SHEsis software to calculate whether the genotype frequency distribution is consistent with the Hardy-Weinberg equilibrium law; analyze the correlation between the candidate gene SNPs locus and schizophrenia; analyze the linkage disequilibrium and haplotypes between the various loci of the gene; use the MDR software to analyze the interaction between the gene and the gene, and the application of SPSS17. 0 software analysis of the correlation between the candidate gene SNPs locus and clinical symptoms and cognitive function of schizophrenia.
1, H-W balance test and linkage disequilibrium analysis
(1) H-W balance test
The genotype distribution of the rs4340, rs3829787 and rs5275 loci in the first schizophrenic group deviated from the H-W balance; the genotype distribution of the rs1800497, rs3829787 and rs1801133 loci was deviated from the H-W balance in the chronic schizophrenia group, indicating that these loci may be susceptible to the disease, or to susceptible SNPs, and other loci genotypes. The cloth was consistent with the H-W equilibrium law (all, P > 0.05) in the first schizophrenic group, the chronic schizophrenia group and the healthy control group, indicating that the sample samples in this study were in accordance with the genetic analysis.
(2) analysis of the degree of linkage disequilibrium
Rs689466 and rs5275 are in highly unbalanced chromosomal regions, indicating that they are located in the linkage disequilibrium region.
2, case control analysis
(1) Single SNP analysis in first-episode schizophrenia-normal control group
Rs141116007 and rs5275 loci were associated with schizophrenia. The frequency distribution of alleles and genotypes in the case group and the control group were significantly different (all, P0.05).Rs2239050 and rs3829787 sites may be associated with schizophrenia, the frequency of.Rs2239050 alleles and the frequency of rs3829787 genotypes in the case group There was a significant difference between the control group and the control group (both, P0.05).
(2) Single SNP analysis in chronic schizophrenia-normal control group
Rs4340, rs1801133 and rs748806 loci were associated with schizophrenia. The allele and genotype frequency distribution in the two groups showed significant differences (all, P0.05).Rs1800497 locus may be associated with schizophrenia, and its genotype frequency distribution was significantly different in the case group and the control group (P0.05).
(3) haplotype analysis in case control group
The combined analysis of 2 SNPs loci of the COX-2 gene showed that only rs689466 (C) -rs5275 (A) as a protective haplotype was associated with first episode schizophrenia (P0.05).
3. Correlation between SNPs and clinical symptoms of schizophrenia
(1) correlation analysis between SNPs and clinical symptoms of first-episode schizophrenia
In the first episode of schizophrenia, the rs141116007 locus of DBH gene and the rs1946518 locus of the IL18 gene were related to the positive symptoms of first schizophrenia and the total score of clinical symptoms (all, P0.05), and the rs4340 site of the ACE gene was associated with the negative symptoms of first episode schizophrenia (P0.05).
(2) correlation analysis between SNPs and clinical symptoms of chronic schizophrenia
In chronic schizophrenia, the COX-2 gene rs689466 and rs5275 loci are related to the positive symptoms of chronic schizophrenia (both, P0.05); the rs2958182 locus of the TCF4 gene is associated with the negative symptoms of chronic schizophrenia (P0.05), and the IL-18 gene rs1946518 locus is associated with the total score of the clinical symptoms of chronic schizophrenia (P0.05).
4, SNPs and the correlation analysis of cognitive function
(1) Correlation between SNPs and Cognitive Function of Normal Healthy Persons
In normal healthy controls, the rs2239050 loci of the TCF4 gene rs2958182 and CACNA1C genes are related to the cognitive function of normal healthy people (both, P0.05); the COX-2 gene rs5275 loci is related to the language of normal healthy people (P0.05); the rs2958182 locus of the TCF4 gene is associated with the delayed memory and total score of cognitive function of normal healthy people. Both, P0.05.
(2) correlation between SNPs and cognitive function in first-episode schizophrenia
In the first episode of schizophrenia, the DBH gene rs141116007, the rs1800497 locus of the DRD2 gene, and the rs5275 locus of the COX-2 gene are associated with the immediate memory of the cognitive function of the first schizophrenia (all, P0.05), and the rs689466 and rs5275 loci of the COX-2 gene are related to the language of the cognitive ability of first episode schizophrenia.
(3) correlation between SNPs and cognitive function in chronic schizophrenia
In chronic schizophrenia, the rs18001133 locus of the MTHFR gene and the rs1800872 locus of the IL-10 gene are related to the attention ability of chronic schizophrenia (both, P0.05), and the TCF4 gene rs2958182 site and the MTHFR gene rs18001133 locus are related to the language ability of chronic schizophrenia (both, P0.05); The 58182 locus is associated with delayed memory of cognitive function of chronic schizophrenia (both, P0.05), and the rs2958182 locus of the TCF4 gene is associated with the total score of cognitive function of chronic schizophrenia (P0.05).
conclusion
From the above analysis, we can get the following conclusions: (1) DBH, COX-2, CHRNA5 and CACAN1C genes may be the susceptible genes of first onset schizophrenia; (2) ACE, DRD2, MTHFR and GNB1L genes may be the susceptible genes of chronic schizophrenia; (3) the COX-2 genes in DBH, IL-18 genes and chronic schizophrenia in first episode schizophrenia are respectively and positive. Symptoms related (; 4) the TCF4 gene of ACE gene and chronic schizophrenia in first episode schizophrenia was associated with negative symptoms respectively. (5) the IL-18 gene of DBH, IL-18 and chronic schizophrenia in first episode schizophrenia was related to the total score of clinical symptoms, and (6) TCF4, CACNA1C and COX-2 genes and the cognitive function work of normal healthy people. Can be related; (7) DBH, DRD2 and COX-2 genes are associated with cognitive function of first episode schizophrenia (; 8) MTHFR, IL-10, DRD2, TCF4 genes are associated with cognitive function of chronic schizophrenia. (9) there is genetic and clinical heterogeneity in schizophrenia.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R749.3
本文編號(hào)：2147118
[Abstract]:Schizophrenia is the most common and most serious mental disease, mostly in young and young adults. The prevalence rate of the world population is about 1%. The main manifestations are the disharmony between mental activity and the realistic environment, the disharmony of cognition, emotion, will and personality. The main causes of schizophrenia are two major causes of environment and heredity. The results of the study of the family, the twins and the mailing seed all showed that the genetic factors played an important role in the disease. The genome scan and candidate gene study of schizophrenia have obtained a lot of positive results, but the reproducibility is poor and the result is very controversial. The clinical symptoms and cognitive functions of schizophrenia are affected by many factors, and their genetic causes are affected. It's going to get a lot of attention.
objective
Using bioinformatics, molecular genetics and biometric methods, the association of DBH, ACE, COMT, DRD2, CHRNA5, IL-10, IL-18, COX-2, TCF4, CACNA1C, MTHFR and GNB1L candidate genes to schizophrenia, on the other hand, to examine whether these effects affect the clinical symptoms and cognitive functions of the subjects and try to reveal the mental points. Susceptibility genes and genetic mechanisms affecting clinical symptoms and cognitive functions.
Method
In this study, 350 cases of first onset schizophrenia, 567 chronic schizophrenia and 421 healthy controls were studied. Schizophrenic patients came from the hospitalized Department of Beijing Hui Long Guan Hospital, and the normal healthy population came from the local community. All the subjects were Chinese Han people, and the patients with seminal schizophrenia had to meet the ICD-10 and CCMD-II-R diagnosis. Break the standard.
In the case of informed consent of the subjects, the peripheral venous blood was collected and the DNA kit was extracted with Promega (USA) liquid, and the genomic DNA. was extracted by PCR-AFLP and SequenomMassArray technology to detect the 13 SNPs loci of the 12 candidate genes (rs141116007, rs4340, rs4680, rs1800497, rs3829787. 958182, rs2239050, rs1801133 and rs748806).
The application of online genetic statistical SHEsis software to calculate whether the genotype frequency distribution is consistent with the Hardy-Weinberg equilibrium law; analyze the correlation between the candidate gene SNPs locus and schizophrenia; analyze the linkage disequilibrium and haplotypes between the various loci of the gene; use the MDR software to analyze the interaction between the gene and the gene, and the application of SPSS17. 0 software analysis of the correlation between the candidate gene SNPs locus and clinical symptoms and cognitive function of schizophrenia.
1, H-W balance test and linkage disequilibrium analysis
(1) H-W balance test
The genotype distribution of the rs4340, rs3829787 and rs5275 loci in the first schizophrenic group deviated from the H-W balance; the genotype distribution of the rs1800497, rs3829787 and rs1801133 loci was deviated from the H-W balance in the chronic schizophrenia group, indicating that these loci may be susceptible to the disease, or to susceptible SNPs, and other loci genotypes. The cloth was consistent with the H-W equilibrium law (all, P > 0.05) in the first schizophrenic group, the chronic schizophrenia group and the healthy control group, indicating that the sample samples in this study were in accordance with the genetic analysis.
(2) analysis of the degree of linkage disequilibrium
Rs689466 and rs5275 are in highly unbalanced chromosomal regions, indicating that they are located in the linkage disequilibrium region.
2, case control analysis
(1) Single SNP analysis in first-episode schizophrenia-normal control group
Rs141116007 and rs5275 loci were associated with schizophrenia. The frequency distribution of alleles and genotypes in the case group and the control group were significantly different (all, P0.05).Rs2239050 and rs3829787 sites may be associated with schizophrenia, the frequency of.Rs2239050 alleles and the frequency of rs3829787 genotypes in the case group There was a significant difference between the control group and the control group (both, P0.05).
(2) Single SNP analysis in chronic schizophrenia-normal control group
Rs4340, rs1801133 and rs748806 loci were associated with schizophrenia. The allele and genotype frequency distribution in the two groups showed significant differences (all, P0.05).Rs1800497 locus may be associated with schizophrenia, and its genotype frequency distribution was significantly different in the case group and the control group (P0.05).
(3) haplotype analysis in case control group
The combined analysis of 2 SNPs loci of the COX-2 gene showed that only rs689466 (C) -rs5275 (A) as a protective haplotype was associated with first episode schizophrenia (P0.05).
3. Correlation between SNPs and clinical symptoms of schizophrenia
(1) correlation analysis between SNPs and clinical symptoms of first-episode schizophrenia
In the first episode of schizophrenia, the rs141116007 locus of DBH gene and the rs1946518 locus of the IL18 gene were related to the positive symptoms of first schizophrenia and the total score of clinical symptoms (all, P0.05), and the rs4340 site of the ACE gene was associated with the negative symptoms of first episode schizophrenia (P0.05).
(2) correlation analysis between SNPs and clinical symptoms of chronic schizophrenia
In chronic schizophrenia, the COX-2 gene rs689466 and rs5275 loci are related to the positive symptoms of chronic schizophrenia (both, P0.05); the rs2958182 locus of the TCF4 gene is associated with the negative symptoms of chronic schizophrenia (P0.05), and the IL-18 gene rs1946518 locus is associated with the total score of the clinical symptoms of chronic schizophrenia (P0.05).
4, SNPs and the correlation analysis of cognitive function
(1) Correlation between SNPs and Cognitive Function of Normal Healthy Persons
In normal healthy controls, the rs2239050 loci of the TCF4 gene rs2958182 and CACNA1C genes are related to the cognitive function of normal healthy people (both, P0.05); the COX-2 gene rs5275 loci is related to the language of normal healthy people (P0.05); the rs2958182 locus of the TCF4 gene is associated with the delayed memory and total score of cognitive function of normal healthy people. Both, P0.05.
(2) correlation between SNPs and cognitive function in first-episode schizophrenia
In the first episode of schizophrenia, the DBH gene rs141116007, the rs1800497 locus of the DRD2 gene, and the rs5275 locus of the COX-2 gene are associated with the immediate memory of the cognitive function of the first schizophrenia (all, P0.05), and the rs689466 and rs5275 loci of the COX-2 gene are related to the language of the cognitive ability of first episode schizophrenia.
(3) correlation between SNPs and cognitive function in chronic schizophrenia
In chronic schizophrenia, the rs18001133 locus of the MTHFR gene and the rs1800872 locus of the IL-10 gene are related to the attention ability of chronic schizophrenia (both, P0.05), and the TCF4 gene rs2958182 site and the MTHFR gene rs18001133 locus are related to the language ability of chronic schizophrenia (both, P0.05); The 58182 locus is associated with delayed memory of cognitive function of chronic schizophrenia (both, P0.05), and the rs2958182 locus of the TCF4 gene is associated with the total score of cognitive function of chronic schizophrenia (P0.05).
conclusion
From the above analysis, we can get the following conclusions: (1) DBH, COX-2, CHRNA5 and CACAN1C genes may be the susceptible genes of first onset schizophrenia; (2) ACE, DRD2, MTHFR and GNB1L genes may be the susceptible genes of chronic schizophrenia; (3) the COX-2 genes in DBH, IL-18 genes and chronic schizophrenia in first episode schizophrenia are respectively and positive. Symptoms related (; 4) the TCF4 gene of ACE gene and chronic schizophrenia in first episode schizophrenia was associated with negative symptoms respectively. (5) the IL-18 gene of DBH, IL-18 and chronic schizophrenia in first episode schizophrenia was related to the total score of clinical symptoms, and (6) TCF4, CACNA1C and COX-2 genes and the cognitive function work of normal healthy people. Can be related; (7) DBH, DRD2 and COX-2 genes are associated with cognitive function of first episode schizophrenia (; 8) MTHFR, IL-10, DRD2, TCF4 genes are associated with cognitive function of chronic schizophrenia. (9) there is genetic and clinical heterogeneity in schizophrenia.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R749.3
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