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【求助】审稿人的意见

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这个帖子发布于6年零124天前，其中的信息可能已发生改变或有所发展。

问题已解决悬赏丁当:5

本人写了一篇meta分析关于基因多态性的。审稿人意见回来了，有一条不是很清楚，请大家帮忙看看。还有allele flipping是什么意思啊。
MAFs are very different among different populations. And some of the MAFs are very close to 0.5. It would be good to add a paragraph in the discussion as to how an MAF close to 0.5 might possibly influence the results due to allele flipping etc.

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2014-11-03 15:43 浏览 : 901 回复 : 6

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一般认为MAF小于0.05就是次等位基因频率过低，没有分析价值，但为什么审稿人认为是0.5 是不是审稿人搞错误了我该怎么回答呢

2014-11-03 15:48

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• 三脑室占位，MR平扫+增强，有病理结果（一周后公布病理）

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还有一个解释是MAF越接近0.5，说明不同的变异位点的如196a2中的C和T存在几率就是一样的，说明在人群中的变异就越多，这种变异就越有研究意义。不知道怎么回答。

2014-11-03 15:49

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• 个人基本健康数据很重要

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满意答案

等位基因翻转？
Aspects of observing and claiming allele flips in association studies.
Clarke GM1, Cardon LR.
Author information
1Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom. gclarke@well.ox.ac.uk
Abstract
Significant allele flipping, where associations for the same disease occur at opposite alleles of the same bi-allelic locus, is increasing. But when is a significant allele flip genuine? We address the statistical issues of claiming and observing genuine allele flips in actual samples. We show that unless an allele flip is genuine, the probability of observing a significant allele flip in samples ascertained similarly from a common population is negligible. We derive expressions for the expected values of commonly used measures of association, which confirm previous findings that the underlying mechanism of a genuine allele flip is variation in the haplotype frequencies and show further how this variation interacts with variation in the genetic effects to impact allele flipping. We show that for association testing at proxy SNPs, common in genome-wide association studies, variation in haplotype frequencies must coincide with a reversal in the sign of linkage disequilibrium (LD) to trigger genuine allele flips. Using HapMap data and r, rather than r(2), to highlight previously unobserved effects, we show that unless genetic effects are large, variation in LD is unlikely to cause genuine allele flips in samples drawn from the same population. However, as populations diverge, it is an increasingly viable cause of a genuine allele flip for sufficiently large genetic effect and/or sample sizes. We conclude that evidence of variation in local patterns of LD, ancestral composition of study samples, and environmental exposures between study populations can provide compelling practical evidence in defense of a genuine allele flip.
PMID: 20013941 [PubMed - indexed for MEDLINE]

2014-11-03 16:14

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• 盆腔肿物，少见病例，病理出来了，请你诊断

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