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

Abstract

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.

Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with Mycobacterium Bovis

“…By searching the human GWAs catalog, we found that PC-esterase domain containing 1BP ( PCED1B ), a hydrolase involved in macrophage apoptosis and autophagy, and ArfGAP With SH3 Domain , Ankyrin Repeat And PH Domain 1 ( ASAP1 ) were the only candidate genes identified in our study that were previously associated with human tuberculosis [ 75 ]. PCED1B was also previously associated with bovine respiratory disease susceptibility [ 62 ].…”

“…Interestingly, the PCED1B, a hydrolase involved in apoptosis and autophagy of infected macrophages, was identified in our study, and it was also associated with human Tb susceptibility [ 75 ]. PCED1B plays a crucial role in apoptosis and autophagy, which are important mechanisms of innate immunity against Mtb [ 86 ].…”

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients

“…Among the 13 datasets, 11 datasets were downloaded from gene expression omnibus (GEO, , accessed on 15 May 2023), 1 dataset was downloaded from the Zenodo repository ( , accessed on 15 May 2023), and 1 more was downloaded from the genome sequence archive (GSA, , accessed on 15 May 2023). The accession numbers were GSE152641 [ 9 ], GSE161731 [ 10 ], GSE161777 [ 11 ], GSE171110 [ 12 ], GSE179850 [ 13 ], GSE185557 [ 14 ], GSE189990 [ 15 ], GSE196822 [ 16 ], GSE213313 [ 17 ], GSE217948 [ 18 ], GSE223885 [ 19 ], Zenodo 6120249 [ 20 ], and HRA000238 [ 21 ].…”