Genome-Wide Association Mapping in Arabidopsis Identifies Previously Known Flowering Time and Pathogen Resistance Genes

Abstract

There is currently tremendous interest in the possibility of using genome-wide association mapping to identify genes responsible for natural variation, particularly for human disease susceptibility. The model plant Arabidopsis thaliana is in many ways an ideal candidate for such studies, because it is a highly selfing hermaphrodite. As a result, the species largely exists as a collection of naturally occurring inbred lines, or accessions, which can be genotyped once and phenotyped repeatedly. Furthermore, linkage disequilibrium in such a species will be much more extensive than in a comparable outcrossing species. We tested the feasibility of genome-wide association mapping in A. thaliana by searching for associations with flowering time and pathogen resistance in a sample of 95 accessions for which genome-wide polymorphism data were available. In spite of an extremely high rate of false positives due to population structure, we were able to identify known major genes for all phenotypes tested, thus demonstrating the potential of genome-wide association mapping in A. thaliana and other species with similar patterns of variation. The rate of false positives differed strongly between traits, with more clinal traits showing the highest rate. However, the false positive rates were always substantial regardless of the trait, highlighting the necessity of an appropriate genomic control in association studies. There is currently tremendous interest in using association mapping to find the genes responsible for natural variation, particularly for human disease. In association mapping, researchers seek to identify regions of the genome where individuals that are phenotypically similar (for example, they all have the same disease) are also unusually closely related. A potentially serious problem is that spurious correlations may arise if the population is structured so that members of a subgroup tend to be much more closely related. Because few genome-wide association studies have been carried out, it is not yet known how important this problem will be in practice. In one of the first genome-wide association studies to date, this paper considers the model plant Arabidopsis thaliana. A very large number of spurious genotype–phenotype correlations are found, especially for traits that vary geographically. For example, plants from northern latitudes flower later; however, in addition to sharing genetic variants that make them flower late, they also tend to share variants across the genome, making it difficult to determine which genes are responsible for flowering. This notwithstanding, several previously known genes were successfully identified in this study, and the researchers are optimistic about the prospects for association mapping in this species.