Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

Abstract

Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes >2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections. Despite their limited application in the field, GWASs have provided valuable insights by pinpointing associations to both innate and adaptive immune response loci, as well as novel unexpected risk factors for infection susceptibility. Herein, we discuss some issues and caveats of GWASs for infectious diseases, we review the most recent findings ensuing from these studies, and we provide a brief summary of selected GWASs for infections in non-human mammals. We conclude that, although the general trend in the field of complex traits is to shift from GWAS to next-generation sequencing, important knowledge on infectious disease-related traits can be still gained by GWASs, especially for those conditions that have never been investigated using this approach. We suggest that future studies will benefit from the leveraging of information from the host's and pathogen's genomes, as well as from the exploration of models that incorporate heterogeneity across populations and phenotypes. Interactions within HLA genes or among HLA variants and polymorphisms located outside the major histocompatibility complex may also play an important role in shaping the susceptibility and response to invading pathogens.

Dynamic linkage of COVID-19 test results between Public Health England’s Second Generation Surveillance System and UK Biobank

“…For rarer risk alleles (1 and 0.1%), the odds ratios detectable with 80 % power increase to 1.6 and 2.9, respectively. While odds ratios of these magnitudes are known for some infection susceptibility variants, many known variants possess more modest odds ratios below 1.2 [ 15, 16 ].…”

Negative regulation ofACE2by interferonsin vivoand its genetic control

“…Epidemiological studies have indicated that the risk for serious disease and death from COVID-19 is higher in males, in older individuals and those with co-morbidities [2][3][4] and it varies across ethnic groups 5 . Host genetic variation is important in determining susceptibility and disease outcome for many infectious diseases 6 and it is likely to be important in determining SARS-COV-2 susceptibility and outcome. Polymorphisms in the host genome could drive differences in ACE2 expression which may affect SARS-CoV-2 susceptibility and infection outcome.…”

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

“…While understanding these signaling pathways is challenging because of the inherent difficulties of studying intracellular pathogens, the specialized nature of the P. falciparum life cycle presents a unique opportunity to explore this issue. A number of reports that suggest coevolution between microbes and hosts can be found in literature (Chapman and Hill, 2012;Mozzi et al, 2018;Quintana-Murci, 2019). The importance of polymicrobial interactions in this occurrence has also been presented (Rioux et al, 2007).…”