臺灣博碩士論文加值系統

收集家庭資料進行疾病與標識基因之相關性研究是近年來遺傳流行病學重要的方法之一。利用親本-染病子代三元體家庭，傳遞不平衡檢定 (transmission/ disequilibrium tests, TDT) 在檢定異質親本中特定對偶基因之傳遞不傳遞機率是否相等。這個方法的好處在於不受群體分層和非隨機交配的影響，然檢定本身未考量遺傳模式對統計量檢定力的影響，是其缺點。目前已有文獻指出在一般致病基因頻率不高，若遺傳模式為隱性模式時，TDT的檢定力不佳。由於檢定數量性狀與候選基因之相關性時，遺傳模式仍是一個干擾源。因此本文提出將此干擾源參數化後，利用親本-子代三元體家庭之條件概似函數 (條件於親代交配型和子代性狀) 推得不同遺傳模式下之計分檢定 (score test) 統計量，並提出二個降低遺傳模式干擾的穩健相關檢定作法。根據模擬結果顯示，這二個檢定在不同遺傳模型下，確實維持一定的檢定力。為遺傳模式未知的研究，提供了一個比較穩健的策略選擇。

Family-based association study is a useful approach for detecting linkage and linkage disequilibrium between a disease gene and a marker in genetic analysis. Using case-parent data the transmission/disequilibrium test (TDT) method tests the equality of the transmission and non-transmission probabilities of a particular maker allele from a heterozygous parent. If the null hypothesis is rejected, it indicates that there is linkage and linkage disequilibrium between the studied disease and the marker loci. Though TDT has been shown as an applicable method in linkage study, its test performance is affected by some nuisances such as gene frequencies, mode of inheritance (MOI) of a disease and linkage disequilibrium between loci. For instance, when the disease allele frequency is low and the disease is recessivity inherited , the power performance of TDT is poor. Theoretically, if we know the actual MOI, the MOI can be involved in the analysis. However, in practice we usually have no idea about the disease mode, and that causes a problem that needs to be addressed. Using robust methods in resoling this problem for a binary trait had been studied. In this paper, we are interested in developing robust methods for handling MOI problem for quantitative traits. By means of conditional likelihoods, we constructed score tests for four modes of inheritance. We then developed two robust procedures to cope with the MOI problem in analysis of quantitative traits. Simulation results showed that our methods truly express robustness property when the actual MOI is unknown.

第一章 緒 論 1-1
第一節 連鎖分析 1-2
第二節 相關分析 1-5
第二章 研究背景及文獻回顧 2-1
第一節 遺傳模式對檢定之干擾 2-1
第二節 數量性狀分析方法 2-6
第三節 以傳遞不傳遞訊息建立之數量性狀分析方法 2-8
第三章 分析數量性狀之穩健相關檢定 3-1
第一節 研究動機及研究目的 3-1
第二節 研究方法 3-3
第三節 常態分布假設下之穩健相關檢定 3-7
第四節 分布來自指數族之穩健相關檢定 3-16
第五節 異質群體下穩健相關檢定的調整作法 3-20
第四章 模擬研究 4-1
第一節 數量性狀具常態分布之檢定力分析 4-2
第二節 數量性狀具伽瑪分布之檢定力分析 4-4
第三節 群體分層結構下之檢定力分析 4-5
第五章 討論與建議 5-1
參考文獻 R-1


附錄
附錄I. 數量性狀為常態分布下，隱性、顯性和
累加模式之計分統計量推導 A-1
附錄II. 計算隱性、累加和顯性模式之計分統計
量相關係數 A-8
附錄III. 數量性狀分布為指數族下，隱性、顯性
和累加模式之計分統計量的推導 A-11

表A.1 – A.7 常態分布下，統計量之檢定力模擬 A-18
表B.1 – B.7 伽瑪分布下，統計量之檢定力模擬 A-25
表C.1 – C.8 群體分層下，統計量之檢定力模擬 A-32

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