Apo-E genotypes and cardiovascular diseases: a sensitivity study using cross-validatory criteria

Biom J. 2005 Aug;47(4):541-53. doi: 10.1002/bimj.200410117.

Abstract

The Apolipoprotein-E (Apo-E) gene, a gene that produces proteins which help to regulate lipid levels in the bloodstream, is of interest in the study of cardiovascular diseases. An approach to making inferences about the genetic effects of the Apo-E gene has been developed by Glickman and Gagnon (2002). The framework describes the role of genetic and risk factors on the onset ages of multiple diseases, and accounts for the possibility that an individual was censored for reasons related to the diseases of interest. The framework also allows for missing genetic information, so that subjects censored prior to genetic sampling, and therefore missing such information, may still be included in the analysis. We apply an extension to this framework to the original cohort of the Framingham Heart Study for measuring the effects of different Apo-E genotypes on the onset age of various cardiovascular disease events. In particular, we compare the fit of univariate versus multivariate onset age components to the model, whether to incorporate health covariates measured at baseline or at a point later in the study, and whether to assume a heritability model for Apo-E genotype frequencies. The results of the best fitting model are presented.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Age of Onset
  • Algorithms*
  • Apolipoproteins E / genetics*
  • Computer Simulation
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / mortality*
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Models, Biological*
  • Models, Statistical
  • Reproducibility of Results
  • Risk Assessment / methods*
  • Risk Factors
  • Sensitivity and Specificity

Substances

  • Apolipoproteins E