The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic

COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The immune system has emerged as a key determinant in shaping the outcome of SARS-CoV-2 infection. It is mainly the deleterious unconstrained immune response, rather than the virus itself, which leads to severe cases of COVID-19 and the associated mortality. Genetic susceptibility to dysregulated immune response is highly likely to be among the host factors for adverse disease outcome. Given that such genetic susceptibility has also been observed in autoimmune diseases (ADs), a number of critical questions remain unanswered; whether individuals with ADs have a significantly different risk for COVID-19–related complications compared to the general population, and whether studies on the genetics of ADs can shed some light on the host factors in COVID-19. In this perspective, we discuss the host genetic factors, which have been under investigation in association with COVID-19 severity. We touch upon the intricate link between autoimmunity and COVID-19 pathophysiology. We put forth a number of autoimmune susceptibility genes, which have the potential to be additional host genetic factors for modifying the severity of COVID-19 presentation. In summary, host genetics at the intersection of ADs and COVID-19 may serve as a source for understanding the heterogeneity of COVID-19 severity, and hence, potentially holds a key in achieving effective strategies in risk group identification, as well as effective treatments.

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Influence of host genetics in shaping the rumen bacterial community in beef cattle

Scientific Reports ◽

10.1038/s41598-020-72011-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Waseem Abbas ◽

Jeremy T. Howard ◽

Henry A. Paz ◽

Kristin E. Hales ◽

James E. Wells ◽

...

Keyword(s):

Bacterial Community ◽

Species Composition ◽

Community Composition ◽

Genetic Factors ◽

Bacterial Community Composition ◽

Gastrointestinal Microbiota ◽

Host Genetics ◽

A Genome ◽

Host Genetic ◽

Host Genetic Factors

Abstract In light of recent host-microbial association studies, a consensus is evolving that species composition of the gastrointestinal microbiota is a polygenic trait governed by interactions between host genetic factors and the environment. Here, we investigated the effect of host genetic factors in shaping the bacterial species composition in the rumen by performing a genome-wide association study. Using a common set of 61,974 single-nucleotide polymorphisms found in cattle genomes (n = 586) and corresponding rumen bacterial community composition, we identified operational taxonomic units (OTUs), Families and Phyla with high heritability. The top associations (1-Mb windows) were located on 7 chromosomes. These regions were associated with the rumen microbiota in multiple ways; some (chromosome 19; position 3.0–4.0 Mb) are associated with closely related taxa (Prevotellaceae, Paraprevotellaceae, and RF16), some (chromosome 27; position 3.0–4.0 Mb) are associated with distantly related taxa (Prevotellaceae, Fibrobacteraceae, RF16, RFP12, S24-7, Lentisphaerae, and Tenericutes) and others (chromosome 23; position 0.0–1.0) associated with both related and unrelated taxa. The annotated genes associated with identified genomic regions suggest the associations observed are directed toward selective absorption of volatile fatty acids from the rumen to increase energy availability to the host. This study demonstrates that host genetics affects rumen bacterial community composition.

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Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

BioMed Research International ◽

10.1155/2013/284729 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 26

Author(s):

Christiane Maria Ayo ◽

Márcia Machado de Oliveira Dalalio ◽

Jeane Eliete Laguila Visentainer ◽

Pâmela Guimarães Reis ◽

Emília Ângela Sippert ◽

...

Keyword(s):

Immune Response ◽

Chagas Disease ◽

Chronic Infection ◽

Genetic Factors ◽

Clinical Course ◽

Clinical Manifestations ◽

Severity Of Disease ◽

Host Genetic ◽

Host Genetic Factors

Chagas disease, which is caused by the flagellate parasiteTrypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during humanT. cruziinfection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC,KIR, and cytokine host genetic factors on the infection byT. cruziand the clinical course of Chagas disease.

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HLA-B∗57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Clinical and Developmental Immunology ◽

10.1155/2011/549023 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Latha Jagannathan ◽

Mrinalini Chaturvedi ◽

Bhuthaiah Satish ◽

Kadappa Shivappa Satish ◽

Anita Desai ◽

...

Keyword(s):

South India ◽

Genetic Factors ◽

Infected People ◽

Gender Influence ◽

Hiv Positive Women ◽

Host Genetic ◽

And Gender ◽

Hiv Seropositive ◽

Host Genetic Factors

Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India.Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control.Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59);P=0.0046;OR=38. CD4 counts also were higher among females in this cohort.Conclusion. This study suggests that HIV positive women with HLA-B*57 have less occurrence of TB as compared to males.

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Genetic aspects of inflammation and cancer

Biochemical Journal ◽

10.1042/bj20071341 ◽

2008 ◽

Vol 410 (2) ◽

pp. 225-235 ◽

Cited By ~ 69

Author(s):

Georgina L. Hold ◽

M. Emad El-Omar

Keyword(s):

Chronic Inflammation ◽

Genetic Factors ◽

Therapeutic Strategies ◽

Signalling Pathways ◽

Neoplastic Progression ◽

Comprehensive Understanding ◽

Host Genetic ◽

Host Genetic Factors ◽

Pro Inflammatory Cytokines

Chronic inflammation is involved in the pathogenesis of most common cancers. The aetiology of the inflammation is varied and includes microbial, chemical and physical agents. The chronically inflamed milieu is awash with pro-inflammatory cytokines and is characterized by the activation of signalling pathways that cross-talk between inflammation and carcinogenesis. Many of the factors involved in chronic inflammation play a dual role in the process, promoting neoplastic progression but also facilitating cancer prevention. A comprehensive understanding of the molecular and cellular inflammatory mechanisms involved is vital for developing preventive and therapeutic strategies against cancer. The purpose of the present review is to evaluate the mechanistic pathways that underlie chronic inflammation and cancer with particular emphasis on the role of host genetic factors that increase the risk of carcinogenesis.

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Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection

Viruses ◽

10.3390/v1020104 ◽

2009 ◽

Vol 1 (2) ◽

pp. 104-125 ◽

Cited By ~ 19

Author(s):

Bertram Bengsch ◽

Robert Thimme ◽

Hubert Blum

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Infection ◽

Genetic Factors ◽

Hepatitis C Virus Infection ◽

Host Genetic ◽

Host Genetic Factors

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Genetic Susceptibility of the Host in Virus-Induced Diabetes

Microorganisms ◽

10.3390/microorganisms8081133 ◽

2020 ◽

Vol 8 (8) ◽

pp. 1133

Author(s):

Keiichiro Mine ◽

Yasunobu Yoshikai ◽

Hirokazu Takahashi ◽

Hitoe Mori ◽

Keizo Anzai ◽

...

Keyword(s):

Type 1 Diabetes ◽

Genetic Susceptibility ◽

Genetic Factors ◽

Target Genes ◽

Host Genetic ◽

Coxsackie B Viruses ◽

Host Genetic Factors ◽

Coxsackie B

Enteroviruses, especially Coxsackie B viruses, are among the candidate environmental factors causative of type 1 diabetes. Host genetic factors have an impact on the development of virus-induced diabetes (VID). Host background, in terms of whether the host is prone to autoimmunity, should also be considered when analyzing the role of target genes in VID. In this review, we describe the genetic susceptibility of the host based on studies in humans and VID animal models. Understanding the host genetic factors should contribute not only to revealing the mechanisms of VID development, but also in taking measures to prevent VID.

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The role of host genetic factors and host immunity in necrotic enteritis

Avian Pathology ◽

10.1080/03079457.2016.1154503 ◽

2016 ◽

Vol 45 (3) ◽

pp. 313-316 ◽

Cited By ~ 17

Author(s):

Sung T. Oh ◽

Hyun S. Lillehoj

Keyword(s):

Genetic Factors ◽

Host Immunity ◽

Necrotic Enteritis ◽

Host Genetic ◽

Host Genetic Factors

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Genetic influences on HIV infection: implications for vaccine development

Sexual Health ◽

10.1071/sh04057 ◽

2005 ◽

Vol 2 (2) ◽

pp. 53 ◽

Cited By ~ 7

Author(s):

Miranda Z. Smith ◽

Stephen J. Kent

Keyword(s):

Hiv Infection ◽

Genetic Factors ◽

Vaccine Development ◽

Critical Role ◽

Genetic Influences ◽

Susceptibility To Infection ◽

Immunodeficiency Virus ◽

Host Genetic ◽

Host Genetic Factors

Human HIV infection is characterised by great variability in outcome. Much of this variability is due either to viral variation or host genetic factors, particularly major histocompatibility complex differences within genetically diverse populations. The study of non-human primates infected with well characterised simian immunodeficiency virus strains has recently allowed further dissection of the critical role of genetic influences on both susceptibility to infection and progression to AIDS. This review summarises the important role of many host genetic factors on HIV infection and highlights important variables that will need to be taken into account in evaluating effective HIV vaccines.

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