請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91805完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李銘仁 | zh_TW |
| dc.contributor.advisor | Ming-Jen Lee | en |
| dc.contributor.author | 周修禾 | zh_TW |
| dc.contributor.author | Hsiu-Ho Chou | en |
| dc.date.accessioned | 2024-02-22T16:48:21Z | - |
| dc.date.available | 2024-02-23 | - |
| dc.date.copyright | 2024-02-22 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-02-16 | - |
| dc.identifier.citation | Reference
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91805 | - |
| dc.description.abstract | 腦內小血管疾病是一種複雜卻常見的神經系統疾病，其特徵是腦內小血管的病理發生變化，是造成中風、認知障礙、和癡呆的主要原因。現階段的挑戰在於了解台灣人群特異性的複雜遺傳結構以及這些基因變異與疾病臨床表現之間的關係。本研究採用了全基因組關聯分析研究，目標為找出潛在的疾病亞型和易感性變異及遺傳異質性問題。研究組別為在國立台灣大學收案之病例樣本(n = 695, 59.2 ±18.3 歲) 與對照組為台灣人體生物資料庫的樣本對比(n = 14,495, 47.8 ± 15.4 歲)，利用自動化分裝試劑儀器Nimbus™) 及自動化晶片儀器(GeneTitan™) 運行Axiom 全基因組TWB 2.0 鑑定晶片分析兩組別之差異。本篇在全基因組關聯性分析研究發現，病例樣本與人體資料庫比較中，在19 號染色體上有10 個顯著差異之單一核苷酸多型性(SNP)，分別位於六個內含子(Intron regions)以及四個基因間隔區(Intergenic regions)。這些SNP 變異和嗅覺受體、代謝酵素和蛋白質受體等基因相關，而其對腦內小血管疾病的病理影響仍然未知。過去研究指出這些基因和動脈粥狀硬化之形成、脂肪代謝、血管功能、或谷氨酸運輸蛋白(glutamate transporter)有關，而這些基因也間接影響腦內小血管產生病變。然而，腦內小血管病變與SNP 及其關聯的這些基因背後的分子機轉仍需再探討研究。整體而言，本篇之關聯性分析研究協助提高了對台灣人群中腦內小血管分子遺傳學的理解，以及SNP 在個體易感於疾病中扮演的潛在角色。這些結果可能為未來疾病預防和個人化的治療策略提供重要資訊。 | zh_TW |
| dc.description.abstract | Cerebral Small Vessel Disease (CSVD) is a prevalent neurological condition characterized by pathological alterations in the small vessels of the brain, which significantly contribute to the incidence of stroke, cognitive decline, and vascular dementia. This study addresses the existing challenges in deciphering the intricate genetic landscape specific to the Taiwanese population and its correlation with the clinical phenotypes of CSVD. Employing a genome-wide association study (GWAS), the research aims to mitigate genetic heterogeneity and identify potential disease subtypes and susceptibility variations.
The study population comprised case samples from National Taiwan University (n = 695, mean age 59.2 ± 18.3 years) and control samples from Taiwan BioBank (n = 14,495, mean age 47.8 ± 15.4 years). Utilizing the Axiom Genome-Wide TWB 2.0 Array Plate on Nimbus™ and GeneTitan™ instruments, followed by PLINK analysis, the GWAS unveiled 10 significant single nucleotide polymorphisms (SNPs) primarily situated on chromosome 19, with predominant occurrences in intronic regions (n = 6) and intergenic regions (n = 4). These identified variants may potentially influence genes encoding protein transporters, metabolic enzymes, and olfactory receptors, some of which are implicated in atherosclerosis, lipid metabolism, and vascular function, thereby potentially exacerbating CSVD. Further elucidation of the underlying biological mechanisms associated with CSVD is imperative. This investigation contributes to an enhanced comprehension of CSVD genetics within the Taiwanese populace, elucidating the role of genetic variants in predisposing individuals to this condition. The insights garnered from this study may inform the development of targeted interventions and personalized treatment modalities in the future. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-02-22T16:48:20Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-02-22T16:48:21Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Table of Contents
Acknowledgements 2 摘要 3 Abstract 4 List of Tables 8 List of Figures 8 List of Abbreviations 9 1. Introduction 11 1.1 Background 11 1.2 Clinical Manifestations and Consequences of CSVD 19 1.3 Pathophysiology of CSVD 24 1.4 Genetics of CSVD 28 1.5 Current Approaches in CSVD Research and Treatments 34 1.6 Research Gaps and Objectives 35 2. Materials and Methods 37 2.1 Study Design 37 2.2 Inclusion criteria for case samples 37 2.3 Exclusion criteria for case samples 39 2.4 Control sample from the Taiwan Biobank 40 2.5 DNA Extraction from Whole Blood and Concentration 41 2.6 Genome-Wide Association Study (GWAS) 42 3. Results 52 3.1 Demographic Data in CSVD GWAS 52 3.2 Study Design Workflow 52 3.3 Participants QC exclusion with heterozygosity and missing rate 54 3.4 Kinship test and relatedness analysis for CSVD GWAS 54 3.5 Principal component analysis (PCA) for CSVD GWAS population 55 3.6 Principal Component Analysis (PCA) between Case-Control Groups 56 3.7 Removal of SNPs with excess missing genotypes 56 3.8 Removal of SNPs with extreme MAF and HWE 57 3.9 Manhattan Plot for CSVD GWAS 57 3.10 Quantile-quantile (QQ) Plot 61 4. Discussion 63 Appendices 73 Reference 90 Supplementary Data 103 | - |
| dc.language.iso | en | - |
| dc.subject | 全基因組關聯分析 | zh_TW |
| dc.subject | 腦內小血管疾病 | zh_TW |
| dc.subject | 蛋白質受體 | zh_TW |
| dc.subject | 代謝酵素 | zh_TW |
| dc.subject | 嗅覺受體 | zh_TW |
| dc.subject | 中風 | zh_TW |
| dc.subject | 單一核苷酸多型性 | zh_TW |
| dc.subject | olfactory receptors | en |
| dc.subject | CSVD | en |
| dc.subject | protein transporters | en |
| dc.subject | metabolic enzymes | en |
| dc.subject | stroke | en |
| dc.subject | SNPs | en |
| dc.subject | GWAS | en |
| dc.title | 台灣族群腦部小血管疾病之全基因組關聯分析: 識別疾病易感性的遺傳風險因子 | zh_TW |
| dc.title | GWAS Analysis of Taiwanese Cerebral Small Vessel Disease (CSVD): Identifying Novel Genetic Loci Contributing to Disease Susceptibility | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 湯頌君;李妮鍾 | zh_TW |
| dc.contributor.oralexamcommittee | Sung-Chun Tang;Ni-Chung Lee | en |
| dc.subject.keyword | 腦內小血管疾病,全基因組關聯分析,單一核苷酸多型性,中風,嗅覺受體,代謝酵素,蛋白質受體, | zh_TW |
| dc.subject.keyword | CSVD,GWAS,SNPs,stroke,olfactory receptors,metabolic enzymes,protein transporters, | en |
| dc.relation.page | 108 | - |
| dc.identifier.doi | 10.6342/NTU202400669 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-02-17 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 分子醫學研究所 | - |
| dc.date.embargo-lift | 2029-01-01 | - |
| 顯示於系所單位： | 分子醫學研究所 | |
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