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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 潘文涵 | zh_TW |
| dc.contributor.advisor | Wen-Harn Pan | en |
| dc.contributor.author | 周承霖 | zh_TW |
| dc.contributor.author | Cheng-Lin Chou | en |
| dc.date.accessioned | 2025-09-17T16:45:29Z | - |
| dc.date.available | 2025-09-18 | - |
| dc.date.copyright | 2025-09-17 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-06 | - |
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Pan, Positive or U-Shaped Association of Elevated Hemoglobin Concentration Levels with Metabolic Syndrome and Metabolic Components: Findings from Taiwan Biobank and UK Biobank. Nutrients, 2022. 14(19). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99812 | - |
| dc.description.abstract | 人體鐵狀況與健康狀態息息相關，涉及範圍甚廣，不論鐵缺乏或過剩都有某些健康效應，理解缺乏與過盛的健康效應之不同，將有助於理解鐵營養之生物意涵。本研究採用雙樣本全表型孟德爾隨機化（Phenome-wide MR），探討遺傳推估之鐵狀況在台灣人群對各種健康結果之因果影響。
本研究使用一大型東亞族群（n=245,062）的血紅素（Hemoglobin）統合分析找到的23,883個與血紅素相關之單核苷酸多態性指標（Single-nucleotide polymorphism, SNP），透過嚴格的統計標準來確保獨立性以及遺傳工具強度，然後使用鐵蛋白（Ferritin）和eQTL數據驗證其與鐵代謝的生物學相關性，篩選出四個鐵狀況遺傳工具變數組成遺傳估計推估鐵狀況指標；再使用臺灣精準醫療計畫資料檢驗其對1,102個臨床表型的因果效應。 分析結果顯示，遺傳估計鐵過剩與骨關節炎、骨折、顱內出血及情緒障礙的風險增加有因果關聯；對貧血則具有保護作用，並與較低的糖化血色素（HbA1c）相關。這些發現為鐵營養對人體健康的廣泛影響提供生物學證據，顯示鐵質雖為必需元素，應避免其缺乏，但較高的鐵質狀況亦可能涉及多種疾病的病程發展。本研究強調了維持鐵質恆定、鐵營養適中，以及在此領域精準營養應用之重要性。 | zh_TW |
| dc.description.abstract | Systemic iron status is critical for health, with both deficiency and excess leading to a wide range of adverse outcomes, yet its causal effects remain unclear due to limitations in observational studies.
This study employed a Two-sample Phenome-wide Mendelian randomization (Phenome-wide MR) to investigate the causal landscape of genetically-proxied iron status across a wide range of health outcomes in Taiwanese population. Using four genetic instruments for iron status, which were filtered from 23,883 candidates based on stringent statistical and biological criteria, from a large East Asian hemoglobin meta-analysis (n=245,062), we tested for causal effects across 1,102 clinical phenotypes with the Taiwan Precision Medicine Initiative statistics. These four instruments were curated from 23,883 candidates by applying stringent statistical filters for independence and strength, and were subsequently validated for biological relevance to iron metabolism using ferritin and eQTL data. Our analysis revealed that a genetic predisposition to higher iron status was causally associated with an increased risk of osteoarthritis, bone fractures, intracranial hemorrhage, and mental disorders. Conversely, it was strongly protective against anemia and associated with lower HbA1c. These findings provide biological evidence for the widespread, pleiotropic effects of iron, demonstrating that while it is essential for maintaining health, excess iron status is a causal risk factor for diverse diseases. This underscores the critical importance of balanced iron homeostasis and cautions against indiscriminate supplementation and highlights the need for precision nutrition strategies to optimize iron status. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-17T16:45:29Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-17T16:45:29Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 目次
中文摘要 i Abstract ii 目次 iv 圖次 v 表次 vi Introduction 1 Function of Iron in human body 1 Metabolism of Iron 2 Measurement of iron state 6 Deficiency and excess of iron nutriture 10 Mendelian Randomization (MR) 12 Current status of large-scale GWAS studies on iron status 17 Current status of PheWAS studies on iron status and outcomes 19 Methods 21 Data Sources 21 Instrumental Variables Selection and Quality Control 22 Statistical Analysis 24 Sensitivity Analyses 24 Results Categorization and Visualization 25 Software 26 Results 27 Discussion 35 Limitations 46 Reference 49 Supplementary Figure 58 | - |
| dc.language.iso | en | - |
| dc.subject | 血紅素 | zh_TW |
| dc.subject | 鐵狀態 | zh_TW |
| dc.subject | 因果推斷 | zh_TW |
| dc.subject | 全表型研究 | zh_TW |
| dc.subject | 孟德爾隨機化 | zh_TW |
| dc.subject | Iron Status | en |
| dc.subject | Hemoglobin | en |
| dc.subject | Causal Inference | en |
| dc.subject | Phenome-wide Study | en |
| dc.subject | Mendelian Randomization | en |
| dc.title | 以雙樣本全表型 MR 探討基因推估鐵狀況之因果效應 | zh_TW |
| dc.title | A Two-sample Phenome-wide MR Investigation on Causal Effects of Genetically-Proxied Iron Status | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 林甫容;陳弘昕 | zh_TW |
| dc.contributor.coadvisor | Fu-Jung Lin;Hung-Hsin Chen | en |
| dc.contributor.oralexamcommittee | 張榮素;陳建勳 | zh_TW |
| dc.contributor.oralexamcommittee | Jung-Su Chang;Chien-Hsiun Chen | en |
| dc.subject.keyword | 鐵狀態,血紅素,孟德爾隨機化,全表型研究,因果推斷, | zh_TW |
| dc.subject.keyword | Iron Status,Hemoglobin,Mendelian Randomization,Phenome-wide Study,Causal Inference, | en |
| dc.relation.page | 64 | - |
| dc.identifier.doi | 10.6342/NTU202504128 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-08-12 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | N/A | - |
| Appears in Collections: | 生化科技學系 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-113-2.pdf Restricted Access | 2.92 MB | Adobe PDF |
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