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Apo‐E Genotypes and Cardiovascular Diseases: A Sensitivity Study Using Cross‐validatory Criteria
Author(s) -
Glickman Mark E.,
Kao MeiFang
Publication year - 2005
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/bimj.200410117
Subject(s) - univariate , framingham heart study , covariate , apolipoprotein e , genotype , missing heritability problem , heritability , logistic regression , missing data , multivariate statistics , disease , framingham risk score , biology , statistics , medicine , bioinformatics , oncology , genetics , gene , single nucleotide polymorphism , mathematics
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. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)