title: On the genetic interpretation of disease data.
abstract: BACKGROUND
  The understanding of host genetic variation in disease resistance increasingly requires the use of field data to obtain sufficient numbers of phenotypes. We introduce concepts necessary for a genetic interpretation of field disease data, for diseases caused by microparasites such as bacteria or viruses. Our focus is on variance component estimation and we introduce epidemiological concepts to quantitative genetics.
  
  
  RESULTS
  We have derived simple deterministic formulae to predict the impacts of incomplete exposure to infection, or imperfect diagnostic test sensitivity and specificity on heritabilities for disease resistance. We show that these factors all reduce the estimable heritabilities. The impacts of incomplete exposure depend on disease prevalence but are relatively linear with the exposure probability. For prevalences less than 0.5, imperfect diagnostic test sensitivity results in a small underestimation of heritability, whereas imperfect specificity leads to a much greater underestimation, with the impact increasing as prevalence declines. These impacts are reversed for prevalences greater than 0.5. Incomplete data recording in which infected or diseased individuals are not observed, e.g. data recording for too short a period, has impacts analogous to imperfect sensitivity.
  
  
  CONCLUSIONS
  These results help to explain the often low disease resistance heritabilities observed under field conditions. They also demonstrate that incomplete exposure to infection, or suboptimal diagnoses, are not fatal flaws for demonstrating host genetic differences in resistance, they merely reduce the power of datasets. Lastly, they provide a tool for inferring the true extent of genetic variation in disease resistance given knowledge of the disease biology.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, United Kingdom. Stephen.Bishop@roslin.ed.ac.uk
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bishop
authors.forename: John A
authors.initials: JA
authors.lastname: Woolliams
mesh_terms: D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D012680:Sensitivity and Specificity