TY - JOUR T1 - Highly epistatic genetic architecture of root length in <em>Arabidopsis thaliana</em> JF - bioRxiv DO - 10.1101/008789 SP - 008789 AU - Jennifer Lachowiec AU - Xia Shen AU - Christine Queitsch AU - Örjan Carlborg Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/09/04/008789.abstract N2 - Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. This is despite the fact that non-additive genetic effects, such as epistatic interactions and developmental noise, are also likely to make important contributions to the phenotypic variability. Analyses beyond additivity require additional care in the design and collection of data, and introduce significant analytical and computational challenges in the statistical analyses. Here, we have conducted a study that, by focusing on a model complex trait that allows precise phenotyping across many replicates and by applying advanced analytical tools capable of capturing epistatic interactions, overcome these challenges. Specifically, we examined the genetic determinants of Arabidopsis thaliana root length, considering both trait mean and variance. Analysis of narrow-and broad-sense heritability of mean root length identified a large contribution of non-additive variation and a low contribution of additive variation. Also, no loci were found to contribute to mean root length using a standard additive model based genome-wide association analysis (GWAS). We could, however, identify one locus regulating developmental noise and seven loci contributing to root-length through epistatic interactions, and four of these were also experimentally confirmed. The candidate locus associated with root length variance contains a candidate gene that, when mutated, appears to decrease developmental noise. This is particularly interesting as most other known noise regulators in multicellular organisms increase noise when mutated. The mutant analysis of candidate genes within the seven epistatic loci implicated four genes in root development, including three without previously described root phenotypes. In summary, we identify several novel genes affecting root development, demonstrate the benefits of advanced analytical tools to study the genetic determinants of complex traits, and show that epistatic interactions can be a major determinant of complex traits in A. thaliana. ER -