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首页> 外文期刊>Journal of applied statistics >Choosing between per-genotype, per-allele, and trend approaches for initial detection of gene-disease association
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Choosing between per-genotype, per-allele, and trend approaches for initial detection of gene-disease association

机译：在按基因型，等位基因和趋势方法之间进行选择，以初步检测基因-疾病关联

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摘要

There are a number of approaches to detect candidate gene-disease associations including: (ⅰ) 'per-genotype', which looks for any difference across the genotype groups without making any assumptions about the direction of the effect or the genetic model; (ⅱ) 'per-allele', which assumes an additive genetic model, i.e. an effect for each allele copy; and (ⅲ) linear trend, which looks for an incremental effect across the genotype groups. We simulated a number of gene-disease associations, varying odds ratios, allele frequency, genetic model, and deviation from Hardy-Weinberg equilibrium (HWE) and tested the performance of each of the three methods to detect the associations, where performance was judged by looking at critical values, power, coverage, bias, and root mean square error. Results indicate that the per-allele method is very susceptible to false positives and false negatives when deviations from HWE occur. The linear trend test appears to have the best power under most simulated scenarios, but can sometimes be biased and have poor coverage. These results indicate that of these strategies a linear trend test may be best for initially testing an association, and the per-genotype approach may be best for estimating the magnitude of the association.
机译：有多种检测候选基因疾病关联的方法，包括：（ⅰ）'每个基因型'，它寻找基因型组之间的任何差异，而无需对效果的方向或遗传模型做任何假设； （ⅱ）“等位基因”，它假设一个附加的遗传模型，即每个等位基因拷贝的作用； （ⅲ）线性趋势，寻找整个基因型组之间的增量效应。我们模拟了许多基因-疾病关联，不同的比值比，等位基因频率，遗传模型以及与Hardy-Weinberg平衡（HWE）的偏差，并测试了三种检测关联的方法的性能，其中性能由查看临界值，功效，覆盖率，偏差和均方根误差。结果表明，当与HWE发生偏差时，按等位基因方法很容易出现假阳性和假阴性。线性趋势测试在大多数模拟情况下似乎都具有最好的功效，但有时可能会产生偏差并且覆盖范围较差。这些结果表明，在这些策略中，线性趋势测试可能最适合于最初测试关联，而每个基因型方法可能最适合于估计关联的大小。

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  • 来源
    《Journal of applied statistics》 |2009年第6期|633-646|共14页
  • 作者

    Ammarin Thakkinstian; John R. Thompson; Cosetta Minelli; John Attia;

  • 作者单位

    Clinical Epidemiology Unit, Faculty of Medicine, Mahidol University, Bangkok, Thailand Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, Newcastle, Australia;

    Centre for Biostatistics and Genetic Epidemiology, Department of Health Sciences, University of Leicester, Leicester, UK;

    Centre for Biostatistics and Genetic Epidemiology, Department of Health Sciences, University of Leicester, Leicester, UK;

    Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, Newcastle, Australia;

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  • 正文语种 eng
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  • 关键词

    per-genotype; per-allele; power; bias; gene-disease association;

    机译：每个基因型等位基因功率;偏压;基因疾病关联;

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