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基因组疾病风险单倍型段的置换筛选检验

ALI Fadhaa , 张健   

  1. 数学、统计及精算学学院, 肯特大学,英格兰肯特郡坎特伯雷市,英国
  • 出版日期:2015-12-25 发布日期:2016-01-12

ALI Fadhaa,张健. 基因组疾病风险单倍型段的置换筛选检验[J]. 系统科学与数学, 2015, 35(12): 1402-1417.

ALI Fadhaa,ZHANG Jian. SCREENING TESTS FOR DISEASE RISK HAPLOTYPE SEGMENTS IN GENOME  BY USE OF PERMUTATION[J]. Journal of Systems Science and Mathematical Sciences, 2015, 35(12): 1402-1417.

SCREENING TESTS FOR DISEASE RISK HAPLOTYPE SEGMENTS IN GENOME  BY USE OF PERMUTATION

ALI Fadhaa ,ZHANG Jian   

  1. School of Mathematics, Statistics and Actuarial Science, University of Kent, Canterbury, England
  • Online:2015-12-25 Published:2016-01-12

通过测试的一群而不是单个的变异与疾病的关联捕获变 异的集体行为,文章提出了单倍型关联分析.这种分析通常涉及未知 相位多位置基因型在病例和对照组中稀疏频率.它从推断单倍型基因 型,共同分类和边际筛查疾病相关的基因单倍型开始.不幸的是,解未 知相位的不确定性可能对单倍型共同分类 (因此对预测风险单倍型的精度) 产生强烈影响. 在这里, 为了解决这一问题, 文章提出一个替代办法: 在阶段一中,选择风险基因型而不是共同分类推断单 倍型.在阶段二中,从前一阶段选择风险基因型推断出风险单 体型.采用仿真研究和实际 数据分析评定提议的程序性能.相比现有的多个 $Z$-检验程序,通过使用建议的程序可增加全基因组关联研究的功效.

The haplotype association analysis has been proposed to capture the collective behavior of sets of variants by testing the association of each set instead of individual variants with the disease. Such an analysis typically involves a list of unphased multiple-locus genotypes with potentially sparse frequencies in cases and controls. It starts with inferring haplotypes from genotypes followed by a haplotype co-classification and marginal screening for disease-associated haplotypes. Unfortunately, phasing uncertainty may have a strong effects on the haplotype co-classification and therefore on the accuracy of predicting risk haplotypes. Here, to address the issue, we propose an alternative approach: In Stage 1, we select potential risk genotypes instead of co-classification of the inferred haplotypes. In Stage 2, we infer risk haplotypes from the genotypes inferred from the previous stage. The performance of the proposed procedure is assessed by simulation studies and a real data analysis. Compared to the existing multiple $Z$-test procedure, we find that the power of genome-wide association studies can be increased by using the proposed procedure. This research was supported by a grant from the Iraq Government.

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[1] 高绍根;李国英;郑伟谋. 识别剪切位点的分组权重矩阵方法[J]. 系统科学与数学, 2007, 27(1): 51-58.
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