Infectious diseases are often affected by specific pairings of hosts and pathogens and therefore by both of their genomes. The integration of a pair of genomes into genome-wide association mapping can provide an exquisitely detailed view of the genetic landscape of complex traits. We present a statistical method, ATOMM (Analysis with a Two-Organism Mixed Model), that maps a trait of interest to a pair of genomes simultaneously; this method makes use of whole-genome sequence data for both host and pathogen organisms. ATOMM uses a two-way mixed-effect model to test for genetic associations and cross-species genetic interactions while accounting for sample structure including interactions between the genetic backgrounds of the two organisms. We demonstrate the applicability of ATOMM to a joint association study of quantitative disease resistance (QDR) in the Arabidopsis thaliana-Xanthomonas arboricola pathosystem. Our method uncovers a clear host-strain specificity in QDR and provides a powerful approach to identify genetic variants on both genomes that contribute to phenotypic variation.
CITATION STYLE
Wang, M., Roux, F., Bartoli, C., Huard-Chauveau, C., Meyer, C., Lee, H., … Bergelson, J. (2018). Two-way mixed-effects methods for joint association analysis using both host and pathogen genomes. Proceedings of the National Academy of Sciences of the United States of America, 115(24), E5440–E5449. https://doi.org/10.1073/pnas.1710980115
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