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標題: | 探討臺灣族群心血管疾病與情緒疾患之基因相關性 Exploring the genetic correlation of cardiovascular diseases and mood disorders in Taiwan |
作者: | Wan-Yu Liao 廖婉羽 |
指導教授: | 盧子彬(Tzu-Pin Lu) |
關鍵字: | 心血管疾病,情緒疾患,基因相關性,單核苷酸多型性, cardiovascular disease,mood disorder,genetic correlation,single-nucleotide polymorphism (SNP), |
出版年 : | 2020 |
學位: | 碩士 |
摘要: | 研究背景:流行病學研究發現心血管疾病患者中情緒疾患的共病盛行率高達24.5%,情緒疾患患者也有較高的心血管疾病發生率與死亡率,顯示出心血管疾病與情緒疾患具有相關性。在基因研究方面,過去心血管疾病與情緒疾患的全基因體關聯性研究(Genome-wide association study, GWAS)結果顯示在此兩類疾病中有許多致病基因是重疊的,如CACNA1C基因被發現同時與心律不整及躁鬱症有關。因此本研究欲針對臺灣族群探討心血管疾病與情緒疾患的共通遺傳變異位點,以了解兩者之間是否具有關聯性。 研究目的:本研究預期以連鎖不平衡分數迴歸分析(LD score regression, LDSC)來評估臺灣族群在心血管疾病與情緒疾患之間的基因相關性。 研究方法:本研究針對3種心血管疾病、12個心臟代謝相關表現型與2種常見的情緒疾患進行全基因體關聯性研究獲得摘要統計量(summary statistics),再進行連鎖不平衡分數迴歸分析。心血管疾病與心臟代謝相關表現型的研究對象來自臺灣人體生物資料庫(Taiwan biobank, TWBB),本研究共包含20,046位參與者,其基因數據經插補後共有46,428,577個變異位點被納入分析。情緒疾患之病例則來自臺灣的四間醫療院所,並以臺灣人體資料庫之參與者作為對照組。我們依據不同種類的情緒疾患以及定序平台共進行了四組全基因體關聯性研究(情緒疾患:13,105位研究對象,5,462,558個變異位點;憂鬱症-TWB1晶片平台:6,760位研究對象,5,447,443個變異位點;憂鬱症-TWB2晶片平台:2,545位研究對象,5,447,443個變異位點;躁鬱症:6,977位研究對象,5,440,510個變異位點)。連鎖不平衡分數(LD score)的計算方面,是以千人基因組計畫(1000 Genome Project)的東亞族群(East Asian population, EAS)作為參考族群進行計算,最後利用全基因體關聯性研究得到的摘要統計量對連鎖不平衡分數(LD score)建立迴歸模型,以估算兩兩表現型間的基因相關性。 研究結果:本研究共針對19個表現型(phenotype)的摘要統計量進行LDSC分析,評估心血管疾病、心臟代謝相關表現型與情緒疾患的基因相關性,但分析結果並不符合預期,在心血管疾病與情緒疾患的基因相關性方面,並沒有發現達統計上顯著差異的結果(CVD vs MD: rg=0.713, S.E.=0.683, P=0.296; CVD vs MDD-TWB1: rg=0.618, S.E.=1.596, P=0.699; CVD vs MDD-TWB2: rg=0.312, S.E.=0.675, P=0.644)。然而,在心血管疾病與其他心臟代謝相關表現型之基因相關性分析,則發現心律不整與身體質量指數之基因相關性為高度正相關,並且達到統計上顯著差異(rg=0.756, S.E.=0.375, P=0.044)。 結論:透過評估心血管疾病與情緒疾患的基因相關性,我們得以更了解共同的遺傳因素對於這兩大複雜疾的影響,然而本篇研究顯示臺灣族群之心血管疾病與情緒疾患間沒有明顯的基因相關性,可能是因為在本研究中納入的樣本之疾病狀態多為自我回報(self-report),錯分(misclassification)的情形對研究結果造成嚴重的干擾,因此未來仍需透過其他研究以較嚴謹的疾病定義來驗證此結果。 Background. Epidemiological studies have revealed the associations between cardiovascular diseases (CVDs) and mood disorders (MDs). However, the underlying mechanism in common to the two diseases remains unclear. Previous genome-wide association studies (GWASs) have identified several genes related to both CVDs and MDs such as CACNA1C in cardiac arrhythmia and bipolar disorder. Therefore, whether genetic factors play an important role in the comorbidity of the two types of diseases deserve further investigations. Objective. This study aims to quantify the effects of the genetic correlation between CVDs and MDs by using the linkage disequilibrium (LD) score regression in the Taiwanese population. Materials and methods. To obtain the summary statistics of CVDs and MDs for further LD score regression modeling, a total of 19 GWASs were conducted for cardiometabolic traits (CM traits), CVDs and MDs. The GWASs of CM traits were performed by using a total of 20,046 participants and 46,428,577 SNPs from Taiwan Biobank (TWBB). Major depressive disorder (MDD) and bipolar disorder (BPD) cases were recruited from four hospitals and medical centers in Taiwan, and healthy individuals from TWBB were randomly selected to serve as the control group. We performed 4 GWASs by different MD subtypes and genotyping platforms (MD: 13,105 participants and 5,462,558 SNPs; MDD-TWB1 platform: 6,760 participants and 5,447,443 SNPs; MDD-TWB2 platform: 2,545 participants and 5,447,443 SNPs; BPD: 6,977 participants and 5,440,510 SNPs). As for the LD score calculation, 1000 Genome Project East Asian (EAS) population was used as the reference panel. Lastly, a regression model was utilized to summarize the test statistics from those analyzed GWASs to the LD scores for two traits selected from the CM traits and MDs in order to evaluate their genetic correlations. Results. We found insignificant genetic associations among all combinations of CM traits and MD phenotypes (CVD vs MD: rg=0.713, S.E.=0.683, P=0.296; CVD vs MDD-TWB1: rg=0.618, S.E.=1.596, P=0.699; CVD vs MDD-TWB2: rg=0.312, S.E.=0.675, P=0.644). Furthermore, arrhythmia showed a positive genetic association with body mass index (rg=0.756, S.E.=0.375, P=0.044) from the CM traits and CVDs. Conclusion. Our findings suggested mild genetic correlations between CM traits and MD in the Taiwanese population. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52309 |
DOI: | 10.6342/NTU202002594 |
全文授權: | 有償授權 |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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