Testing implications of the polygenic model for the genetic analysis of loci identified through genome-wide association

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 statementQuantitative traits are similarly likely influenced by randomly picked loci as by loci identified in a genome-wide association study.