From genotypes to genes: Doubling the sample size
From genotypes to genes: Doubling the sample size
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DOI：
10.2307/2533494
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发表时间：
1997-12-01
期刊：
影响因子：
1.9
通讯作者：
Sasieni, PD
中科院分区：
文献类型：
--
作者：
Sasieni, PD
本文考虑对遗传性病例 - 对照数据进行分析。一种方法是考虑病例组和对照组的等位基因频率。因为在任何常染色体位点上每个人都有两个等位基因，所以等位基因的数量将是人数的两倍。另一种方法是考虑在那些不具有所关注等位基因（A）的个体、具有单个拷贝（杂合子）的个体以及对A为纯合子的个体中患病的风险。第三种方法不区分具有一个或两个A拷贝的个体。当通过血清学方法确定等位基因且无法区分纯合子与具有一个A拷贝和一个未知等位基因的个体时，这种情况很常见。这三种方法在文献中都有使用，但这是对它们进行的首次系统性比较。探讨了此类分析中优势比的不同解释，并给出了前两种方法渐近等效的条件。讨论了这三种方法的卡方统计量。当哈迪 - 温伯格平衡成立时，将等位基因而非基因型作为个体实体进行分析所得到的优势比和卡方统计量才是合适的。当平衡成立时，基于等位基因的检验统计量渐近等同于使用基因型数据进行的趋势检验。因此，不应使用将等位基因而非个体作为观察对象的分析方法。相反，我们建议应按基因型对这类数据进行分析。
This paper considers the analysis of genetic case-control data. One approach considers the allele frequency in cases and controls. Because each individual has two alleles at any autosomal locus, there will be twice as many alleles as people. Another approach considers the risk of the disease in those who do not have the allele of interest (A), those who have a single copy (heterozygous), and those who are homozygous for A. A third approach does not differentiate between individuals with one or two copies of A. This was common when alleles were determined serologically and one could not distinguish between homozygotes and those with one copy of A and one of an unknown allele. All three approaches have been used in the literature, but this is the first systematic comparison of them. The different interpretations of the odds ratios from such analyses are explored and conditions are given under which the first two approaches are asymptotically equivalent. The chi-squared statistics from the three approaches are discussed. Both the odds ratio and the chi-squared statistic from the analysis that treats alleles rather than genotypes as individual entities are appropriate only when the Hardy-Weinberg equilibrium holds. When the equilibrium holds, the allele-based test statistic is asymptotically equivalent to the test for trend using the genotype data. Thus, analyses that treat alleles rather than people as observations should not be used. Instead, we recommend that such data should be analyzed by genotype.