A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies.
A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies.
复制标题
从基因组广泛关联研究获得的候选基因结果的务实建议。
DOI：
10.1186/1471-2156-8-20
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发表时间：
2007-05-10
期刊：
影响因子：
2.9
通讯作者：
Knight, Jo
中科院分区：
文献类型：
--
作者：
Curtis, David;Vine, Anna E.;Knight, Jo
在充分调查候选区域之前，研究人员可能会着手进行全基因组关联研究，这些候选区域已被报道产生证据表明它们含有易感位点。如果没有进行全基因组研究，那么候选区域只有适度统计意义的结果将被认为是有趣的，并将刺激进一步的研究。然而，如果键入数十万个标记，那么不可避免地会出现大量这样的结果，而那些来自候选区域的结果可能不会引起特别注意。提出了一种方法，其中对候选区域的标记和在基因组宽扫描的背景下常规键入的标记进行差异处理。对两种类型的标记分配不同的先验概率。从每个标记的报告p值推导出似然比，计算为LR = echiinv(1,p)/2，并获得支持真正关联的后验几率。这些几率可用于对标记进行排序，以提示需要进一步基因分型的区域。我们建议指定先验概率，使得p = 0.01显著的候选标记和p = 0.00001显著的常规标记将产生相似的后验赔率值。我们表明，这可以通过将候选标记的先验关联概率值设置为0.1和常规标记的0.00018来实现。必须采用正式程序，以避免候选区域的适度积极结果被大量名义上显著的结果所淹没，这些结果将在非常多的标记进行基因分型时获得。进行从p值到后验概率的转换的软件可从。
Researchers may embark on a genome-wide association study before fully investigating candidate regions which have been reported to produce evidence to suggest that they harbour susceptibility loci. If the genome wide study had not been carried out then results which demonstrated only modest statistical significance from candidate regions would be judged to be of interest and would stimulate further investigation. However if hundreds of thousands of markers are typed then inevitably very large numbers of such results will occur by chance and those from candidate regions may attract no special attention. An approach is proposed in which differential treatment is afforded to markers from candidate regions and from those that are routinely typed in the context of a genome wide scan. Different prior probabilities are assigned to the two types of marker. A likelihood ratio is derived from the reported p value for each marker, calculated as LR = echiinv(1,p)/2, and the posterior odds in favour of a true positive association are obtained. These odds can be used to rank the markers with a view to suggesting the regions in which further genotyping is indicated. We suggest that prior probabilities be specified such that a candidate marker significant at p = 0.01 and a routine marker significant at p = 0.00001 will yield similar values for the posterior odds. We show that this can be achieved by setting a value for prior probability of association to 0.1 for candidate markers and to 0.00018 for routine markers. It is essential that formal procedures be adopted in order to avoid modestly positively results from candidate regions being swamped by the huge number of nominally significant results which will be obtained when very many markers are genotyped. Software to carry out the conversion from p values to posterior odds is available from .
影响因子：
9.8
作者：
Roeder, K;Bacanu, SA;Devlin, B
通讯作者：
Devlin, B
影响因子：
30.8
作者：
Pe'er, Itsik;de Bakker, Paul I. W.;Daly, Mark J.
通讯作者：
Daly, Mark J.