研究背景
先前有研究認為複雜疾病會受到遺傳和生活環境兩者相互作用的影響，基因-環境交互作用主要是在研究基因遺傳與環境因素會對疾病造成什麼樣的影響。氣喘是由基因-環境交互作用的複雜疾病，全基因組關聯分析結果表示有些基因有助於氣喘的發展，但遺傳作用的效果並不強，可能部分會受到環境因子影響。

研究目的
氣喘這項疾病常發生英國與台灣人身上，本研究目的為探索哪些基因和環境因素會影響氣喘的發生。進而針對英國生物資料庫和台灣人體資料庫中的基因與環境交互作用做族群差異之氣喘比較。

方法
本研究主要使用英國生物資料庫，探討氣喘這項疾病的基因-環境交互作用。使用全基因組關聯分析，找出與氣喘相關的SNPs，再使用基因風險評分計算遺傳風險，以及歸納出環境因子分數。進而評估英國生物資料庫中患有氣喘的風險，並與已發表的台灣人體資料庫結果相比較。

結果 
在疾病組與對照組不同參數設定的基因風險評分下，兩組皆有顯著統計上的差異。當基因風險評分越高，得到氣喘的勝算比越高。利用基因風險評分與環境因子評分組成基因-環境因子交互作用的羅吉斯回歸模型可以辨別出是否得到氣喘。

結論
此研究主要是針對英國生物資料庫進行氣喘研究，並與台灣生物資料庫做比較。在過去研究發現，台灣生物資料庫中有氣喘的人通常帶有rs2304053和rs215274這兩個SNPs，與本研究英國生物資料庫中找到的SNPs不同。可能的原因為，英國生物資料庫參與的主要研究人種大多為英國人，根據不同地區及人種的人體生物資料庫會有族群差異，可知氣喘疾病存在族群差異，因此，本研究結果所找到的SNPs較適用於解釋英國人。此外，我們找到久坐時間、2005年NO2、2010年PM10及社經地位指數對氣喘具有顯著的基因-環境交互作用關係。

Backgroung：
Previous studies have suggested that complex diseases are affected by gene and environment (G×E) interactions. Asthma is a complex disease caused by G×E interactions. The results of genome-wide association studies (GWAS) have shown that some genes contribute to the development of asthma. However, the genetic effect have a weak influence on asthma, and may be partially affected by environmental factors.

Purpose：
Asthma is a disease often occurs in British and Taiwanese. The purpose of this study is to explore which genes and environmental factors affect the occurrence of asthma. Furthermore, this study compared the G×E interactions in Taiwan Biobank (TWB) and the UK Biobank (UKB) to determine the differences of the ethnic groups.

Method：
This study mainly used UKB to explore G×E interactions of asthma. Firstly, we used GWAS to find out SNPs related to asthma in UKB. Secondly, we calculated polygenic risk score (PRS) and environmental factor scores in UKB. Thirdly, we identified G×E interactions of asthma in UKB. Finally, we compared UKB results with the previously published TWB findings.

Result：
Under the PRS set by different parameters between the case group and the control group, there are significant statistical differences between the two groups. In our study, we found that the higher the PRS value, the higher the risk of getting asthma. Furthermore, using the PRS and environmental factor scores to form a logistic regression model of G×E interactions, it can be distinguished whether asthma is obtained.

Conclusion：
This study mainly focuses on asthma research in UKB, and compares it with previous TWB findings. Past studies have found that people with asthma in Taiwan’s biological database usually carry two SNPs, rs2304053 and rs215274, which are different from the SNPs found in UKB GWAS results in this study. The possible reason is that most of the main research races involved in UKB are British. According to different regions and races, the biobanks will have ethnic differences. It can be seen that there are ethnic differences in asthma. Therefore, the results of this study found the SNPs in UKB are more suitable for explaining British. In addition, we found that sedentary time, 2005 NO2, 2010 PM10, and Townsend deprivation index have significant gene-environment interactions on asthma in UKB.

目錄I
表目錄II
圖目錄III
第一章 緒論	1
1.1 研究背景與動機	1
1.2 研究目的	2
1.3 研究架構	3
第二章	文獻探討	4
第三章	資料介紹	9
3.1 資料來源	9
3.1.1英國生物資料庫(UK Biobank)	10
3.2主要環境因子	12
第四章	研究方法	18
4.1主要環境因子	18
4.2資料品質管制(Quality Control, QC)	18
4.3常態檢定	19
4.3.1 Anderson-Darling test (AD test)	19
4.3.2 Lilliefors test (LF test)	19
4.4平均數檢定	20
4.4.1 Mann-Whitney U test (M-W test)	20
4.5全基因組關聯分析(Genome-Wide Association Studies, GWAS)	20
4.6 Clumping	21
4.7基因風險評分(Polygenic Risk Score, PRS)	21
4.8環境因子綜合分數	22
4.9基因環境交互作用(Gene-environment interaction)	23
第五章	研究結果	24
第六章	結論	39
6.1 總結與討論	39
6.2 未來研究	39
參考文獻	40
附錄	42
 
表目錄
表2.1氣喘相關共病與環境因子之研究	5
表3.1.1 疾病分布狀況	9
表3.1.2 研究對象基本資料	11
表3.2 環境因子	13
表4.2.1 Plink QC指令	19
表4.5 Plink association指令	20
表4.6 Plink clump指令	21
表4.7 Plink PRS指令	21
表4.8環境因子	22
表5.1 clump結果	24
表5.2 Anderson-Darling test	29
表5.3 Lilliefors test	29
表5.4 Mann-Whitney U test	29
表5.5 Group 1基因風險評分分組比較	30
表5.6 Group 2基因風險評分分組比較	30
表5.7 分類後之環境因子	33
表5.8 基因-環境(久坐時間)交互作用模型	36
表5.9 基因-環境(2005年NO2)交互作用模型	37
表5.10 基因-環境(2010年PM10)交互作用模型	37
表5.11 基因-環境(社經地位指數)交互作用模型	38
 
圖目錄
圖1.1研究流程圖	3 
圖5.1 Group1病例組和對照組之基因風險評分分布圖	25
圖5.2 Group 2病例組和對照組之基因風險評分分布圖	25
圖5.3 Group 1基因風險評分QQ plot	26
圖5.4 Group 2基因風險評分QQ plot	26
圖5.5 Group 1病例組之基因風險評分QQ plot	27
圖5.6 Group 1對照組之基因風險評分QQ plot	27
圖5.7 Group 2病例組之基因風險評分QQ plot	28
圖5.8 Group 2對照組之基因風險評分QQ plot	28

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