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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭柏秀 | |
| dc.contributor.author | Mei-Hsin Su | en |
| dc.contributor.author | 蘇美心 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:16:59Z | - |
| dc.date.available | 2025-03-12 | |
| dc.date.copyright | 2020-03-12 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-02-24 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65038 | - |
| dc.description.abstract | 自殺是一項重要的公共衛生議題，同時也是台灣主要死因排名的第 11 位。自殺的成因相當複雜，包含了生理、心理、病理、及環境等因素的交互作用。在眾多複雜的成因中，心理因素之一的人格特質在過去研究中被發現：即使個案經歷到相同的環境或病理因素，但自殺的風險卻會因人格特質的不同而有顯著的差異。說明了人格在自殺議題中扮演著修飾因子的角色。除此之外，遺傳
及分子精神病學相關的研究紛紛發現某些遺傳因子與人類行為的失調(包括自殺)相關。因此本研究第一即是探討人格特質與自殺意念與自殺企圖的相關性、第二是以全基因掃描的方式找出與自殺企圖相關的遺傳因子，並且計算人格的多基因風險分數，探討人格的基因分數與自殺企圖的相關性。第三是計算自殺的多基因風險分數，並利用此分數找出帶有較多自殺相關遺傳因子之極度高風險個案，進一步在極度高風險個案中尋找可能的保護因子。本研究結果發現，在人格分數中，神精質及傷害畏避分數較高者會有較高的風險出現自殺意念及自殺企圖，且人格對於自殺的影響與是否患有精神疾患是獨立的。另外，研究結果也發現神精質人格分數可以將企圖自殺者從儘具有意念的個案中分別出來。至於全基因掃描及多基因風險評分的研究結果則發現，在情感性疾患的病人中，rs7708072 之位點(位於 NNT-AS1 基因之上) 與自殺企圖有顯著相關且也自殺企圖的盛行率會隨著神精質及盡責性這兩項人格的基因風險分數的提高而增加。在保護因子的分析中則發現，男性、發病年齡愈晚的情感性疾患、以及家庭支持等因素在極高風險的個案中會是自殺的保護因子。建議未來可將神精質人格及自殺之多基因風險分數合併考慮，用以作為鑑別自殺高風險個案之指標。 | zh_TW |
| dc.description.abstract | Suicide ideation (SI) and suicide attempt (SA) are important public health issues worldwide and suicide is the 11th leading cause of death in Taiwan. Among the complex contributions to suicide, personality is a moderater when subjects experience the same psychopathological or environmental factors. In addition, SA-related markers have been widely reported in genetic and molecular psychiatry studies. Hence the first aim of this study is to investigate the effect of single and combination traits of personality (neuroticism (N), extraversion (E), harm avoidance (HA), and novelty seeking (NS) were included) on SI and SA. Second, we conducted a genome-wide association study (GWAS) for SA in mood disorder patients to identify SA-related markers. Also, we calculated the polygenic risk score (PRS) of personality (E, N, conscientiousness (C) and openness (O) were included) and then examine the association between personality PRS and SA. Finally, we used PRS of SA
(PRSsa) to identify subjects who carried more SA-related genetic markers and detect possible protective factors. In the results, we found higher N or HA are associated with increased risk of SI and SA, and the effect of personality traits is independent of mood disorder diagnosis. We also found higher N score further distinguishes attempters from ideators among mood disorder patients. For GWAS analysis, rs7708072 in NNT-AS1 gene met genomewide significance in mood disorder patients and an upward trend of SA prevalence was associated with increasing PRS of N and C. Male gender, later onset age of mood disorder and family support are protective factors of SA in the top 20% of PRSsa group. Target on identifying a high risk group to investigate further the mechanisms underlying the link between resilience factors and suicidal behaviors for suicide prevention will be valuable for future study. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:16:59Z (GMT). No. of bitstreams: 1 ntu-109-D00849003-1.pdf: 2436198 bytes, checksum: 1cc39a534d33c50ad0edc427105b1333 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員審定書 i
中文摘要 ii Abstract iii Chapter 1 Introduction 1 1.1 Suicidal behavior is a crucial public health issue 1 1.1.1 Epidemiology of suicidal behaviors 1 1.1.2 Contributing factors to suicidal behaviors 2 1.1.3 Introduction of personality 3 1.1.4 Personality and suicide 6 1.1.5 Personality is a moderator of suicide 7 1.2 The associations between personality, suicide and mood disorder 7 1.2.1 Personality is associated with human behavior and decision making 7 1.2.2 Mood disorder patients are high-risk group for suicidal behaviors 10 1.2.3 The associations between mood disorder and personality 10 1.3 Biological backgrounds for mood disorder, personality and suicide 11 1.3.1 Neurotransmitters regulate mood disorder, personality, and suicide 11 1.3.2 Neurotransmitters is regulated by genetic factors 12 1.4 Genetic effect on suicide 14 1.4.1 Candidate gene studies 14 1.4.2 Genome-wide association study (GWAS) for suicide 15 1.4.3 Polygenic risk score for suicide 16 1.5 Specific Aims 17 Chapter 2 Material and Methods 20 2.1 Research design and method 20 2.2 Study participant 22 2.2.1 Part I: examing the association between personality and suicide 22 2.2.2 Part II: genetic analysis 23 2.2.3 Part III: detecting protective factors of SA 24 2.3 Measurement for suicide 24 2.3.1 Part I: examing the association between personality and suicide 24 2.3.2 Part II: genetic analysis 25 2.3.3 Part III: detecting protective factors of SA 25 2.4 Measurement for Personality Traits 26 2.5 Laboratory materials 27 2.5.1 DNA extraction 27 2.5.2 Genome-wide genotyping 27 2.5.3 Imputation and quality control (QC) 28 2.6 Statistics Analysis 28 2.6.1 Association between personality and suicidal behaviors 28 2.6.2 Genome-wide association for suicide attempt (SA) 29 2.6.3 Polygenic risk scores (PRS) calculation 29 2.6.4 Detecting protective factors in subjects who carried more SA-related genetic variants 31 Chapter 3 Results 33 3.1 The Associations between personality and suicidality and SA discrimination 33 3.1.1 The prevalence of suicidal behaviors in Taiwan 33 3.1.2 The association between personality and suicidality 34 3.1.3 Using personality traits to distinguish attempters from ideators 35 3.2 Identify SA-related genetic variants using GWAS 36 3.2.1 A case-only analysis 36 3.2.2 Attempters with mood disorder vs. Taiwan Biobank healthy controls 36 3.3 The association between personality PRS and SA 37 3.3.1 Subjects with higher PRSc had higher SA prevalence 38 3.3.2 The trend of SA prevalence by PRSe was opposite in GPC-2 and 23andMe 38 3.3.3 Higher PRSn increased the prevalence of SA 38 3.3.4 No trend was found for PRSo 38 3.3.5 The positive predictive value of PRSsa 39 3.3.6 SNPs associated with SA and trait N and trait E 39 3.4 The protective factors of SA in subjects who carried more SA-related genetic variants 39 Chapter 4 Discussion 41 4.1 The association between personality and suicide 41 4.2 Trait N can distinguish attempters from ideators 44 4.3 Suicide-Related Genetic Variants 45 4.4 Personality PRS and SA 46 4.4.1 Subjects with higher PRSn are more tended to have SA 46 4.4.2 The trends of SA prevalence were different between PRSe based on GPC-2 and 23andMe 47 4.5 Possible protective factors in subjects who carried more SA-related genetic variants 48 4.5.1 PRSsa based on Caucasian sample may not distinguish attempters in Asia sample 48 4.5.2 Male gender, later age of onset and family support were protective factors of SA, even subjects who carried more risk genetic loci 49 4.5.3 The limitation of using PRS in suicide and personality 51 4.6 Limitation 51 4.7 Conclusion 53 Reference 54 List of Tables Table 1. Demographic variables for each diagnosed group in Part I analysis 66 Table 2. Clinical characteristics of attempters and non-attempters in mood disorder patients 68 Table 3. The correlation coefficients among personality traits 69 Table 4. Logistic regression analysis for the associations between personality and suicidal behaviors 70 Table 5. Stratification analysis for the associations between personality and suicidal behaviors 72 Table 6. LD independent loci (biallelic) associated with suicide attempt in BPD and MDD samples. 73 Table 7. LD independent loci (biallelic) associated with suicide attempt in mood disorder vs. Taiwan Biobank controls (after LD clumping). 75 Table 8. Demographic variables of subjects with top 20% versus last 80% of PRS for SA and possible protective factors of SA in top 20% group 77 List of Figures Figure 1. Flow chart of the study design. 80 Figure 2. Study design of the thesis 81 Figure 3. Combinational effects of pair-wise personality traits on suicidal behaviors 82 Figure 4. Personality profiles for suicide ideation and behaviors 84 Figure 5. Manhattan plot of SA GWAS within-case group 85 Figure 6. Manhattan plot of SA GWAS in mood disorder subjects and community controls 86 Figure 7. The distribution of SA prevalence in different personality PRS group based on GPC-2 88 Figure 8. The distribution of SA prevalence in different personality PRS group based on 23andMe 89 Figure 9. The overlapping rate of genetic loci related to SA and trait N and trait E 91 Supplementary Table S1. Test the differences of SA prevalence in different instruments. 93 Table S2. Genetic correlation of SA and personality traits 94 Table S3. Variance of SA explained on PRSsa 95 Table S4. Genetic markers reported by previous suicide GWAS 96 Table S5. No statistical differences of PRSsa between attempters and non-attempters 97 Table S6. The correlation between scores of trait E/N and their PRS 98 Figure S1. Some overlapped genes were found in both our SA GWAS and ISGC results 99 | |
| dc.language.iso | en | |
| dc.subject | 自殺 | zh_TW |
| dc.subject | 全基因掃描研究 | zh_TW |
| dc.subject | 人格 | zh_TW |
| dc.subject | 情感性疾患 | zh_TW |
| dc.subject | 神精質人格 | zh_TW |
| dc.subject | neuroticism | en |
| dc.subject | genome-wide association study | en |
| dc.subject | personality | en |
| dc.subject | mood disorder | en |
| dc.subject | suicide | en |
| dc.title | 探討人格特質、遺傳因子及保護因子對自殺行為之影響 | zh_TW |
| dc.title | Investigation of the effects of personality, genetic variants and protective factors for suicidal behaviors | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳為堅,蕭朱杏,蔡世仁,廖士程 | |
| dc.subject.keyword | 自殺,全基因掃描研究,人格,情感性疾患,神精質人格, | zh_TW |
| dc.subject.keyword | suicide,genome-wide association study,personality,mood disorder,neuroticism, | en |
| dc.relation.page | 99 | |
| dc.identifier.doi | 10.6342/NTU202000543 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-02-24 | |
| 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 |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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