Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk

Infectious diseases still threaten global human health, and host genetic factors have been indicated as determining risk factors for observed variations in disease susceptibility, severity, and outcome. We performed a genome-wide meta-analysis on 4624 subjects from the 10,001 Dalmatians cohort, with 14 infection-related traits. Despite a rather small number of cases in some instances, we detected 29 infection-related genetic associations, mostly belonging to rare variants. Notably, the list included the genes CD28, INPP5D, ITPKB, MACROD2, and RSF1, all of which have known roles in the immune response. Expanding our knowledge on rare variants could contribute to the development of genetic panels that could assist in predicting an individual's life-long susceptibility to major infectious diseases. In addition, longitudinal biobanks are an interesting source of information for identifying the host genetic variants involved in infectious disease susceptibility and severity. Since infectious diseases continue to act as a selective pressure on our genomes, there is a constant need for a large consortium of biobanks with access to genetic and environmental data to further elucidate the complex mechanisms behind host-pathogen interactions and infectious disease susceptibility.

Automated summary

Infectious diseases remain a threat to global human health, and host genetic factors play a role in determining susceptibility, severity, and outcome. A genome-wide meta-analysis of 4624 subjects was conducted, identifying 29 infection-related genetic associations, primarily rare variants. Notably, genes with known roles in the immune response were detected, suggesting that understanding rare variants could aid in predicting an individual's susceptibility to infectious diseases.