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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭柏秀 | zh_TW |
| dc.contributor.advisor | Po-Hsiu Kuo | en |
| dc.contributor.author | 顏于庭 | zh_TW |
| dc.contributor.author | Yu-Ting Yan | en |
| dc.date.accessioned | 2023-10-03T17:46:22Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-10-03 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-08 | - |
| dc.identifier.citation | 1 Mozaffarian, D. et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 133, e38-360, doi:10.1161/cir.0000000000000350 (2016).
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90821 | - |
| dc.description.abstract | 引言：
缺血性心臟病和憂鬱症是全球主要的失能原因之一，許多研究顯示缺血性心臟病和憂鬱症之間有顯著的關聯。缺血性心臟病患者伴隨憂鬱會導致更差的身體健康結果，這強調了評估此族群憂鬱情況並提供適當支持的重要性。這兩個疾病之間的關聯可能受到遺傳和環境因素的影響。在遺傳學研究中，識別缺血性心臟病患者中高風險憂鬱基因的研究主要集中在單一基因位點上，然而單一基因位點對於複雜性疾病的解釋能力較弱，需要進行全基因組關聯研究來發展多基因風險評分，以預測缺血性心臟病患者憂鬱的風險。本研究旨在識別與憂鬱風險相關的基因位點，並預測缺血性心臟病族群的憂鬱風險。 方法： 本研究使用英國人體生物資料庫樣本，在缺血性心臟病族群及其亞族群（心肌梗塞和男女性別）中進行全基因組關聯分析，以探討與憂鬱風險相關的基因位點。並對有參與追蹤評估憂鬱的族群進行基因組生存分析，以探討與缺血性心臟病患者憂鬱發生有關的基因位點。除此之外，我們還運用了先前大規模全基因組關聯研究的結果，來估算缺血性心臟病患者憂鬱風險的統合多基因風險評分。 結果： 在全基因組關聯分析的結果中，只有一個位點在缺血性心臟病男性族群達到全基因組關聯的顯著水準（p<5×10^(-8)）。我們在缺血性心臟病及其亞族群中識別到一些達到建議顯著水準（p<5×10^(-6)）的位點，在缺血性心臟病族群中有13個，心肌梗塞族群中有47個，缺血性心臟病男性族群中有72個，缺血性心臟病女性族群中有36個。在缺血性心臟病族群中，p-value最小的位點為對應到LOC101927967基因的rs13415804（p=1.17×10^(-7)）。在心肌梗塞族群中，p-value最小的位點為對應到ARMC4和MPP7基因的rs1857620（p=1.26×10^(-7)）。在缺血性心臟病男性族群中，p-value最小的位點為對應到LOC101927967基因的rs13415804（p=2.71×10^(-8)）。在缺血性心臟病女性族群中，p-value最小的位點為對應到DNAJB8、DNAJB8-AS1、GATA2和LOC90246基因的rs11712335（p=6.06×10^(-7)）。在基因組生存分析中，有17個位點達到全基因組關聯的顯著水準，p-value最小的位點為對應到DAPK1基因的rs11141899（p=9.63×10^(-9)）。而統合多基因風險評分的結果顯示高風險分數與憂鬱風險增加有顯著關聯（p=3.43×10^(-9), 勝算比=1.34 [95% 信賴區間 1.22-1.48]）。 結論： 我們的研究使用全基因組關聯分析和全基因組生存分析來識別與缺血性心臟病族群中憂鬱相關的高風險基因。未來的研究需要探討這些基因位點對缺血性心臟病族群中憂鬱的影響。除此之外，統合多基因風險評分方法提供了更好的能力去識別缺血性心臟病族群中憂鬱的高風險個體。 | zh_TW |
| dc.description.abstract | Background
Ischemic heart disease (IHD) and depression are the leading causes of disability worldwide. Numerous studies have shown a significant association between depression and IHD. Comorbid depression in people with IHD leads to worse physical health outcomes, highlighting the importance of assessing and providing appropriate support for depression in this population. The association between depression and IHD may be influenced by genetic and environmental factors. In genetic studies, the identification of genes associated with a high risk of depression in IHD patients has mostly focused on a single-variant. However, the explanatory power of single variants for complex trait disorders such as depression is weak. Genome-wide association studies (GWAS) are needed to develop a polygenic risk score (PRS) to predict the risk of depression in IHD patients. The aim of this study is to identify genetic variants for the risk of depression and predict depression risk in the IHD population. Materials and Methods Our study used the UK Biobank samples to investigate the genetic risk variants associated with the risk of depression in patients with IHD by GWAS in the IHD population and its subgroups, including those with myocardial infarction (MI) and different genders. In addition, we performed genome-wide survival analysis in the follow-up samples to investigate the genetic risk for the incidence of depression in IHD patients. We also calculated the meta-polygenic risk score (metaPRS) for depression in IHD patients by integrating data from several previous large-scale GWAS studies. Results In the GWAS, there was only one single nucleotide polymorphism (SNP) reached the genome-wide significance level (p<5×10^(-8)) in IHD male population. And we found suggestive SNPs (p<5×10^(-6)) in IHD and its subpopulations: 13 in IHD, 47 in MI, 72 in IHD male, and 36 in IHD female. In the IHD population, the SNP with the lowest p-value was rs13415804 (p=1.17×10^(-7)), which mapped to the LOC101927967 gene. In the MI population, the SNP with the lowest p-value was rs1857620 (p=1.26×10^(-7)), which mapped to the ARMC4 and MPP7 genes. In the IHD male population, the SNP with the lowest p-value was rs13415804 (p=2.71×10^(-8)), which mapped to the LOC101927967 gene. In the IHD female population, the SNP with the lowest p-value was rs11712335 (p=6.06×10^(-7)), which mapped to the DNAJB8, DNAJB8-AS1, GATA2 and LOC90246 genes. In the genome-wide survival analysis, there were 17 SNPs at GWAS significant level, the SNP with the lowest p-value was rs11141899 (p=9.63×10^(-9)), which mapped to the DAPK1 gene. The metaPRS results showed a significant association between higher scores and increased odds of depression (p=3.43×10^(-9), OR=1.34 [95% CI 1.22-1.48]). Conclusion: Our study used GWAS and genome-wide survival analysis to identify high-risk genes associated with depression in the IHD population. Future studies are needed to investigate the impact of these genetic variants on depression in the IHD population. In addition, the metaPRS approach offers improved possibilities for identifying individuals at high risk of depression within the IHD population. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-03T17:46:22Z No. of bitstreams: 0 | en |
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| dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 III ABSTRACT V List of Tables IX List of Figures X List of Supplementary Materials XI Chapter 1 Introduction 1 1.1 The epidemiology of IHD and major depressive disorder (MDD): 1 1.2 Relationship between IHD and Depression 1 1.3 Depression in the IHD subpopulation (MI and gender). 2 1.4 The interaction between depression and IHD 3 1.5 Genetic studies of IHD and depression 4 1.6 Study gap 6 1.7 Specific aim 7 Chapter 2 Materials and Methods 8 2.1 UK Biobank 8 2.2 Phenotype data of IHD 8 2.3 Phenotype data of Depression 9 2.4 Follow-up cohort 10 2.5 Townsend deprivation index and other characteristic 10 2.6 Genotyping, imputation and quality control process 11 2.7 Statistical analysis 12 2.7.1 Demographics and clinical characteristic 12 2.7.2 GWAS was conducted in the IHD population and its subpopulations 12 2.7.3 Genome-wide survival analysis was conducted in the IHD follow up cohort 13 2.7.4 Clumping and reporting gene 13 2.7.5 MetaPRS 13 Chapter 3 Results 16 3.1 Demographic characteristics of the study cohort 16 3.2 GWAS for depression in IHD patients 17 3.3 Genome-wide survival analysis for depression among IHD patients during follow-up 19 3.4 Analysis of metaPRS and single-trait PRS 20 Chapter 4 Discussion 22 4.1 Prevalence of lifetime depression among IHD patients 22 4.2 Demographic characteristics 22 4.3 Genes associated with the risk of depression 24 4.3.1 GWAS result in the IHD population 24 4.3.2 GWAS result in the MI population 25 4.3.3 GWAS result in the IHD male population 25 4.3.4 GWAS result in the IHD female population 26 4.4 Gender differences in the depression associated genes 27 4.5 Common SNPs in GWAS of IHD population and subpopulations 28 4.6 Common SNPs in GWAS of IHD population and non-IHD populations 29 4.7 Non-replication of previous candidate gene studies in our GWAS 30 4.8 Genes associated with incident depression during follow-up 30 4.9 The explanatory power of the metaPRS score for depression in the IHD population 31 4.10 Calculation of metaPRS scores after inclusion of IHD-related traits. 32 4.11 Comparison of metaPRS with previous MDD-PRS 33 4.12 Strengths and limitations 34 4.13 Conclusion 35 Reference 36 Tables 45 Figures 52 Supplementary Materials 66 | - |
| dc.language.iso | en | - |
| dc.subject | 全基因組關聯性分析 | zh_TW |
| dc.subject | 統合多基因風險評分 | zh_TW |
| dc.subject | 全基因組生存分析 | zh_TW |
| dc.subject | 缺血性心臟病 | zh_TW |
| dc.subject | 憂鬱 | zh_TW |
| dc.subject | genome-wide survival analysis | en |
| dc.subject | Ischemic heart disease | en |
| dc.subject | metaPRS | en |
| dc.subject | depression | en |
| dc.subject | genome-wide association analysis | en |
| dc.title | 識別缺血性心臟病患者中與憂鬱症有關的遺傳風險變異和多基因風險分數 | zh_TW |
| dc.title | Identification of genetic risk variants and polygenic risk score for depression in patients with ischemic heart disease | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 盧子彬;蕭朱杏;林鴻儒 | zh_TW |
| dc.contributor.oralexamcommittee | Tzu-Pin Lu;Chu-Hsing Hsiao;Hung-Ju Lin | en |
| dc.subject.keyword | 缺血性心臟病,憂鬱,全基因組關聯性分析,全基因組生存分析,統合多基因風險評分, | zh_TW |
| dc.subject.keyword | Ischemic heart disease,depression,genome-wide association analysis,genome-wide survival analysis,metaPRS, | en |
| dc.relation.page | 92 | - |
| dc.identifier.doi | 10.6342/NTU202303607 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2023-08-09 | - |
| dc.contributor.author-college | 公共衛生學院 | - |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | - |
| dc.date.embargo-lift | 2028-08-08 | - |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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