Testing implications of the polygenic model for the genetic analysis of loci identified through genome-wide association
Testing implications of the polygenic model for the genetic analysis of loci identified through genome-wide association
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DOI：
10.1101/639955
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发表时间：
2019-05
期刊：
影响因子：
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通讯作者：
Wenyu Zhang;R. Reeves;D. Tautz
中科院分区：
文献类型：
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作者：
Wenyu Zhang;R. Reeves;D. Tautz
有人提出，许多基因座没有显着的关联，在GWA的研究，仍然可以有助于表型通过修饰符与核心基因的相互作用，这意味着数量性状的多基因决定。我们已经测试了这一假设，使用果蝇蛹表型。我们确定了候选基因蛹长度决定在GWA和显示的基因，大多数确实参与了表型，大概形成了一个核心途径的破坏版本。然后，我们随机选择了低于GWA阈值的基因，发现其中四分之三也对性状产生了影响。我们进一步测试了这些敲除品系对独立的行为蛹性状（化蛹位点选择）的影响，发现它们中类似但不相关的部分也具有显著的影响。因此，我们的数据证实了预测，大量的基因可以影响独立的数量性状。影响陈述数量性状同样可能受到随机挑选的基因座的影响，正如在全基因组关联研究中发现的基因座一样。
It has been proposed that many loci with no significant association in GWA studies can nonetheless contribute to the phenotype through modifier interactions with the core genes, implying a polygenic determination of quantitative traits. We have tested this hypothesis by using Drosophila pupal phenotypes. We identified candidate genes for pupal length determination in a GWA and show for disrupted versions of the genes that most are indeed involved in the phenotype, presumably forming a core pathway. We then randomly chose genes below the GWA threshold and found that three quarters of them had also an effect on the trait. We further tested the effects of these knockout lines on an independent behavioral pupal trait (pupation site choice) and found that a similar, but non-correlated fraction of them had a significant effect as well. Our data thus confirm the prediction that a large number of genes can influence independent quantitative traits. Impact statement Quantitative traits are similarly likely influenced by randomly picked loci as by loci identified in a genome-wide association study.