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Shon, Dewon
01/2002Dissertation
Genetic epidemiology (GE) usually considers the distribution of a disease in family members. The object of this thesis is to interpret estimates of epidemiology parameters (EP) obtained in a GE study in terms of genetic parameters (GP). Specifically we consider a situation where the (1) penetrance of the allele for the disease is low; (2) there is some disease associated trait with a much higher recurrence risk of abnormality in relatives than the disease itself. We define the disease as qualitative and the trait as a bivariate phenotype and we assume a pleiotropic genetic model for this phenotype. The EPs are in the case of a quantitative disease associated trait are the effect size on comparing the mean of cases to mean of controls and mean value in siblings of cases to controls. For a qualitative trait (having two forms, “abnormal” and “normal”) the EPs are the relative risk of abnormality in cases and in siblings as compared to controls. Our goal is to interpret the estimates of EP in terms of GPs for the trait. We determine the algebraic relationship between EP for a quantitative disease associate trait and GPs for the quantitative disease associated trait (heritability of the trait). We also determine the algebraic relationship between the EP for a qualitative trait and the genetic parameters for a qualitative disease associated trait, i.e. penetrance of the abnormality associated with each genotype. Then we propose a method for estimating the genetic parameters from estimates of epidemiologic parameters when given these and the genetic parameters of the disease. We shall present applications to schizophrenia and thought disorder which is a schizophrenia related trait. We also developed a user friendly software for obtaining estimates of genetic parameters when given the estimates of the epidemiologic parameters, disease prevalence and recurrence risk for the disease.
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