利用親本子代三元體家庭之概似函數建立數量性狀基因座定位之穩健相關檢定

Likelihood-based robust association tests for mapping quantitative trait loci using parent-offspring triad data

王俊毅(Jiun-Yi Wang)

指導教授 ： 戴政

國立臺灣大學/公共衛生學院/流行病學研究所/博士(2005年)

https://doi.org/10.6342/NTU.2005.00598

摘要

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。

關鍵字

三元體家庭 ； 傳遞不平衡檢定 ； 數量性狀 ； 連鎖不平衡 ； 遺傳模式 ； 干擾參數 ； 計分檢定統計量 ； 穩健檢定

並列摘要

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.

並列關鍵字

triad family ； transmission/disequilibrium test ； TDT ； quantitative traits ； linkage disequilibrium ； mode of inheritance ； interference parameter ； score test ； robust test

參考文獻

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