Genetic Insights into Population Adaptations Associated with Immunity and Host Defense

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 25 September 2024 | Viewed by 725

Special Issue Editor


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Guest Editor
Department of Neurology, University of California, San Francisco, CA, USA
Interests: genetics and epigenetics; human evolution; single cell multiomics

Special Issue Information

Dear Colleagues,

As pathogens exert significant selective pressure on the human genome, the variability of immune responses across populations becomes evident. Understanding these differences in antiviral and inflammatory responses provides invaluable mechanistic insights into the activation of innate immunity, thus fostering the development of customized therapeutic interventions based on the known genetics.

The dissection of the evolutionary genetics of the immune system provided us with insights into population-specific adaptations related to immunity and host defense. Moreover, the interbreeding between early Eurasian populations and now-extinct hominins such as Neanderthals or Denisovans, along with admixture among modern human populations, has been recognized as advantageous for adapting to pathogen pressures and has partially accounted for disparities in population immune responses. While functional genomics studies increasingly contribute to understanding immune adaptations linked to lifestyle shifts from hunting to gathering, historical population migrations, and past epidemics, few have comprehensively addressed the combined genetic and environmental contributions.

We invite submissions for a Special Issue focused on exploring the intricate relationship between genetic variation, population diversity, and immune responses. This Special Issue aims to compile cutting-edge research that investigates how genetic, epigenetic, and environmental factors contribute to variations in immune responses across diverse human populations. We encourage contributions that illuminate the underlying mechanisms driving population disparities in immune function and explore their implications for human health and disease.

Dr. Cheng I. Wang
Guest Editor

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Keywords

  • population disparities
  • genetic polymorphism
  • human evolution
  • functional genomics
  • immunogenetics
  • transcriptional regulation
  • gene-environment interaction

Published Papers (1 paper)

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Research

10 pages, 3506 KiB  
Article
Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease
by Zoha Kamali, Nafiseh Esmaeil, Chris H. L. Thio, Ahmad Vaez and Harold Snieder
Genes 2024, 15(7), 889; https://doi.org/10.3390/genes15070889 - 6 Jul 2024
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Abstract
Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of [...] Read more.
Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. Methods: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Results: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). Conclusions: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases. Full article
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