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Abstract

Genome-wide association studies are widely used to identify “disease genes” conferring resistance/susceptibility to infectious diseases. Using a combination of mathematical models and simulations, we demonstrate that genetic interactions between hosts and parasites [genotype-by-genotype (G 3 G) interactions] can drastically affect the results of these association scans and hamper our ability to detect genetic variation in susceptibility. When hosts and parasites coevolve, these G 3 G interactions often make genome-wide association studies unrepeatable over time or across host populations. Reanalyzing previously published data on Daphnia magna susceptibility to infection by Pasteuria ramosa, we identify genomic regions consistent with G 3 G interactions. We conclude by outlining possible avenues for designing more powerful and more repeatable association studies.