Abstract

Although genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles. These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. The strongest predictors of levels of genetic variation in susceptibility were disease characteristics negatively associated with immune effectiveness. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful. These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology.

Highlights

  • Genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases

  • A total of 40 diseases were included in the final analyses because for six diseases, we could not find any scientific literature evaluating genetic variation in susceptibility (Table 1)

  • Variation in susceptibility was significantly negatively correlated with effectiveness of vaccine development, with low levels of genetic variation for diseases with an effective vaccine

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Summary

Introduction

Genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology.

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