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研究生:謝宗仁
研究生(外文):Tsung-Jen Hsieh
論文名稱:親本-子代三元體家庭之穩健多變量相關檢定
論文名稱(外文):Robust Multivariate Association Test Using Parent-Offspring Triad Families
指導教授:戴政戴政引用關係
口試委員:陳秀熙鄭明燕丘政民黃冠華
口試日期:2012-11-09
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:流行病學與預防醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2012
畢業學年度:101
語文別:中文
論文頁數:77
中文關鍵詞:候選基因遺傳模式多數量性狀穩健多變量相關檢定
外文關鍵詞:candidate genegenetic modelmultiple quantitative traitsrobust multivariate association test
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為了特徵化一個複雜疾病的遺傳機制,在以家庭為基礎的遺傳研究中,通常會收集多個相關的數量性狀,進行一個假定的基因與多性狀間之多變量相關性分析,來搜尋潛在的疾病基因。雖然這種多變量相關檢定方法相較於單變量相關檢定方法具有較佳的檢定力表現,但是當研究所探討的基因之遺傳模式(或稱作基因顯性程度)設定錯誤時,這些多變量相關檢定方法會遭遇到統計檢定力降低之風險。本論文的主要目的為利用親本-子代三元體家庭資料來發展一個穩健多變量相關檢定,首先將在隱性、可累加或顯性遺傳模式下建立最適多變量計分檢定,再以這些最適檢定來建立一個最大值型態的穩健多變量相關檢定。在模擬研究中,以本論文所提出的方法和現有的多變量方法進行型I錯誤率與檢定力之比較,模擬結果證實穩健多變量相關檢定在所有可能的遺傳模式下,確實表現出檢定力之穩健性。在實例分析中,以一個實際資料來說明本論文所提出的方法之應用性,分析結果顯示當處理多數量性狀時,穩健多變量相關檢定確實較穩健單變量相關檢定更具有檢定能力。

For characterizing the genetic mechanism of a complex disease multiple correlated quantitative traits are usually collected in a genetic study. On the basis of familial data, several multivariate tests have been proposed to investigate the association between the underlying disease genes and the multiple traits. Although these association tests may have better power performance than those univariate association tests, they suffer from loss of testing power when the genetic model (mode of inheritance) of the putative gene is misspecified. In this thesis we aim to develop a robust multivariate association test using parent-offspring triad data. We will first establish the optimal multivariate score test for the recessive, additive or dominant genetic model, based on these optimal tests a maximum-type robust multivariate association test is then proposed. Simulations are conducted to compare our proposed method with the existing multivariate methods on type I error rates and testing powers. The results show that the proposed robust test does manifest the robustness in testing power over all plausible genetic models. A practical data set is also applied to demonstrate the applicability of our proposed approach. The results suggest that the robust multivariate association test is more powerful than robust univariate association test when dealing with multiple quantitative traits.

表目錄 i
圖目錄 iii
第一章 緒論 1
第一節 研究背景 1
第二節 數量性狀的單變量與多變量相關檢定以及穩健單變量相關檢定
之文獻回顧 3
一、變異數成份為基礎的單變量相關檢定 3
二、數量性狀傳遞不平衡為基礎的單變量相關檢定 6
三、以家庭為基礎的多變量相關檢定 10
四、無母數廣義Kendall’s tau為基礎的多變量相關檢定 12
五、最大值方法的穩健單變量相關檢定 13
六、遺傳模式選取的穩健單變量相關檢定 15
第三節 研究目的 18
第二章 研究方法 20
第一節 資料結構 20
第二節 建立親本-子代三元體家庭的條件概似函數 21
第三節 隱性、可累加與顯性模式的最適多變量計分檢定 25
第四節 穩健多變量相關檢定 30
第三章 模擬研究 35
第一節 模擬設定 35
第二節 多變量相關檢定的型I錯誤率與檢定力之比較 37
第三節 在所有顯性程度範域下多變量相關檢定之檢定力表現 39
第四章 實例分析 41
第一節 資料背景 41
第二節 分析結果 43
第五章 討論與建議 46
附錄:隱性、可累加與顯性模式下,最適多變量計分檢定統計量X_2_REC、X_2_ADD與X_2_DOM之推導 49
參考文獻 58


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