The dissection of complex susceptibility to infectious disease: bacterial, viral and parasitic infections

• Main effects in GWAS on viral infections were observed for MHC variants.
• The notable exception is the association of IL28B variants with HCV clearance.
• In leprosy and leishmaniasis strongest effects were obtained for MHC variants.
• In tuberculosis the main effects (TOX, 11p13 locus) are outside the MHC.
• In malaria four susceptibility genes are located outside the MHC.

Infectious diseases are the result of the exposure of susceptible hosts to pathogenic microbes. Genetic factors are important determinants of host susceptibility and efforts are being made to establish the molecular identity of such genetic susceptibility variants by genome-wide association studies. Results obtained to date partly confirm already known genetic vulnerabilities, but also point to new and unexpected mechanisms of susceptibility that extend from classical innate and acquired immunity to weaknesses in constitutional resistance. These studies also revealed an overlap in genetic control between infectious disease and other common immune and inflammatory disorders.