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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81991完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭柏秀(Po-Hsiu Kuo) | |
| dc.contributor.author | Ming-Huan Zeng | en |
| dc.contributor.author | 曾洺澴 | zh_TW |
| dc.date.accessioned | 2022-11-25T05:33:42Z | - |
| dc.date.available | 2026-08-31 | |
| dc.date.copyright | 2021-10-01 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-31 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81991 | - |
| dc.description.abstract | "氧化壓力為體內活性氧物質和抗氧化劑之間無法達成平衡時所產生的現象，此現象與多種不良健康狀況有關，包含癌症、神經退化性疾病、心血管疾病等。過去研究表明，在情緒疾患的患者中觀察到大腦存在氧化壓力的現象，因此氧化壓力在情緒疾患的病理機制中越來越受到關注，而情緒疾患患者通常伴隨著情緒變化、焦慮、睡眠困擾、自殺行為等症狀，由於情緒疾患的多種臨床症狀，診斷存在高度異質性。除了臨床症狀之外，社會心理特質也會增加情緒疾患的風險。然而並非所有過去的研究都顯示氧化壓力基因多型性與情緒疾患之間存在顯著關聯，且鮮少有研究檢查它們對與情緒疾患相關的異質性表現的影響。因此本研究目的為探討氧化壓力基因和情緒相關表徵與社會心理特質的相關性，以更好了解哪些特定表徵可能參與氧化壓力路徑，另外我們也評估氧化壓力基因對歐洲和亞洲人群的影響是否有差異。 本研究使用英國人體生物資料庫，總共納入425,214位受試者來自歐洲族群，平均年齡56.81歲(標準差=7.97)，其中53.90%為女性。表型由5個類別組成，總共包含183個表徵，當中，情緒類別包含82個表徵，焦慮類別有37個表徵，睡眠類別7個表徵，自殺類別19個表徵，以及社會心理類別38個表徵。在基因數據中，總共有10,882個單核苷酸變異(SNP)予以保留在往後的分析，這些SNP位在40個氧化壓力基因。我們使用累加遺傳模型執行羅吉斯和線性回歸模型，模型皆校正性別、年齡、第一至第十主成分，以確定哪些表徵與氧化壓力基因相關。此外我們檢驗表型相關性以檢查和氧化壓力基因顯著相關的表徵之間是否存在高度相關。另一方面，我們使用英國人體生物資料庫中的亞洲人群 (N=6,675) 來評估相關性結果是否在不同族群中存在差異。使用R 版本4.0.2和PLINK 1.9進行統計分析。 我們確定了40個與氧化壓力相關的基因，且將其分為兩類。我們的結果顯示8個基因(GPX1, GPX5, PRDX1, CCS, SOD1, NOX4, NOXA1, NOS1)對於情緒相關表徵與社會心理特質具有顯著的影響。GPX1、GPX5、NOS1和NOXA1基因當中包含9個SNPs (rs11710434, rs111761769, rs6774721, rs1389529156, rs146918648, rs139410431, rs139582054, rs1875140, rs112535944)可能存在多效性。我們發現在183個表徵中有18個在Bonferroni校正後顯示出與氧化壓力基因顯著相關，而這些顯著的關聯都沒有在亞洲人群中複製。另一方面，我們觀察到與氧化壓力基因相關的表徵之間存在中低度相關。 我們找到的SNP中發現了潛在的調控功能，當中有六個是潛在的甲基化數量性狀基因座(mQTL)，可能會影響血液中的DNA甲基化，而其中五個也是可能的表現數量性狀基因座(eQTL)，與人腦或其他組織中的表現量相關。本研究提供了4個氧化壓力基因(包含9個SNP)對歐洲人群的情緒、焦慮、睡眠和社會心理特質的多效性的結果，此外我們發現氧化壓力基因對情緒疾患相關特徵的影響可能存在種族差異。我們的研究提供了情緒疾患的症狀表現異質性可能存在著共同氧化壓力路徑的新見解，未來值得進一步研究調查情緒疾患中和氧化壓力相關的生物學路徑。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T05:33:42Z (GMT). No. of bitstreams: 1 U0001-3108202121080500.pdf: 6973252 bytes, checksum: f49deabed8c854568c2376b86d235d3b (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "誌謝 i 中文摘要 ii ABSTRACT iv CONTENTS vii LIST OF FIGURES ix LIST OF TABLES x Chapter 1 Introduction 1 1.1 Oxidative stress 1 1.1.1 ROS generation 1 1.1.2 Antioxidants 2 1.1.3 The impact of oxidative stress 2 1.2 Mood disorders 3 1.2.1 Heterogeneous presentation in mood disorders 3 1.2.2 Psychosocial factors were associated with mood disorders 4 1.3 Genetic effects on oxidative stress 4 1.4 The associations between oxidative stress and mood disorders 5 1.4.1 Candidate gene studies of ROS generation 5 1.4.2 Candidate gene studies of antioxidants 6 1.5 Aims 7 Chapter 2 Materials and Methods 9 2.1 Study participants 9 2.2 Genotyping, imputation and quality control process 9 2.3 Classification of phenotypes 10 2.3.1 Mood domain 11 2.3.2 Anxiety domain 12 2.3.3 Sleep domain 12 2.3.4 Suicide domain 13 2.3.5 Psychosocial and well-being domain 13 2.4 Gene selection and definitions 14 2.4.1 Oxidative stress genes selection 14 2.4.2 Negative Controls 14 2.4.3 The definition of genomic locations 15 2.5 Gene-based association analysis 15 2.6 Phenotypic correlation analysis 15 2.7 Gene-based association analysis in Asian population 16 2.8 Functional annotation 16 2.9 Sensitivity analysis 17 Chapter 3 Results 18 3.1 Demographics of European and Asian samples 18 3.2 Summary characteristics of five domains 18 3.3 The pleiotropic effects of four oxidative stress genes 19 3.4 The pleiotropic effects of nine SNPs 20 3.5 Potential eQTLs and mQTLs 21 Chapter 4 Discussion 22 4.1 The effects of oxidative stress genes on heterogeneous presentation of mood disorders 22 4.2 Identification of four genes with pleiotropic effects 23 4.3 Identification of nine SNPs with pleiotropic effects on mood related traits and psychosocial factors 25 4.4 The associations between two exon variants and mood related traits 26 4.5 Consideration of the effects of potential comorbidities on oxidative stress 27 4.6 The genetic effects of oxidative stress genes presented in Europeans 28 4.7 Strengths and limitations 29 4.8 Conclusions 30 Supplements 70 Reference 111" | |
| dc.language.iso | en | |
| dc.subject | 異質性症狀表現 | zh_TW |
| dc.subject | 情緒疾患 | zh_TW |
| dc.subject | 活性氧物質 | zh_TW |
| dc.subject | 基因多效性 | zh_TW |
| dc.subject | 抗氧化劑 | zh_TW |
| dc.subject | 氧化壓力 | zh_TW |
| dc.subject | heterogeneous symptoms presentations | en |
| dc.subject | antioxidants | en |
| dc.subject | Oxidative stress | en |
| dc.subject | pleiotropic effects | en |
| dc.subject | mood disorders | en |
| dc.subject | ROS | en |
| dc.title | 探討氧化壓力基因對情緒相關表徵和社會心理特質之多效性 | zh_TW |
| dc.title | Investigating the pleiotropic effects of oxidative stress genes on mood related traits and psychosocial variables | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭朱杏(Hsin-Tsai Liu),盧子彬(Chih-Yang Tseng),陳柏熹 | |
| dc.subject.keyword | 氧化壓力,基因多效性,情緒疾患,異質性症狀表現,活性氧物質,抗氧化劑, | zh_TW |
| dc.subject.keyword | Oxidative stress,pleiotropic effects,mood disorders,heterogeneous symptoms presentations,ROS,antioxidants, | en |
| dc.relation.page | 117 | |
| dc.identifier.doi | 10.6342/NTU202102916 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-09-01 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-31 | - |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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