Keywords:
Acquired immunity; Bacterial infection; Genetic risk factors; Genome-wide association studies (GWAS); Helicobacter pylori; Human leukocyte antigen (HLA); Innate immunity; Leishmaniasis; Leprosy; Major histocompatibility complex (MHC); Malaria; Otitis media; Parasitic infection; Periodontitis; Tuberculosis
Abstract:
Identifying genetic risk factors for bacterial and parasitic infections could provide important leads for improved therapies and vaccines. To date, most candidate gene allelic association and genome-wide linkage studies have been underpowered and/or not replicated. Here we focus on more recent well-powered genome-wide association studies (GWAS), including malaria, leprosy, tuberculosis, and visceral leishmaniasis (VL). Not surprisingly, the beta-hemoglobin gene associated with sickle cell anemia and beta-thalassemia, and the ABO blood group polymorphisms, have achieved genome-wide significance across multiple malaria studies. Of interest too, genome-wide significance for human leukocyte antigen DRB1/DQA1 class II region genes has only been reported for leprosy and VL, and not for tuberculosis. Since class II function lies at the heart of eliciting host CD4+ T cell–mediated immunity, these associations have important implications for vaccine design. For leprosy, 10 out of 12 genes identified through GWAS have also been identified as genetic risk factors for Crohn's disease, supporting the more general hypothesis that host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. This kind of evidence for the interrelationship between autoimmune disease and infectious disease can also only be achieved with confidence in the analysis of well-powered genome-wide studies.