Predicting predisposition of complex disease using genetic information: An application to human hypertension.

Abstract

The purpose of the present study was to determine whether familial or genetic information improves the ability to predict predisposition to hypertension. A predictive model was proposed which evaluated the contribution of information about genotypes, intermediate risk factor traits, demographics and family history toward prediction of an individual's predisposition to hypertension. The first aim of this study tested the null hypothesis that the inclusion of information about genotype does not improve the ability to predict hypertension beyond what is provided by information about biochemical and physiological risk factor traits and concomitants. The second aim of this study tested the null hypothesis that the predictive ability of the model did not improve when information about relatives was included. A risk profile for hypertension was identified. Age was the most consistent predictor of hypertension. Other variables predicted specific forms of hypertension. Males with elevated levels of Na-Li countertransport were predisposed to earlier onset or diastolic hypertension. Males and females with higher lipid levels were predisposed to later onset hypertension that may be associated with systolic blood pressure elevations secondary to atherosclerotic disease. Elevated Na-Li countertransport or elevated apolipoprotein CII in males who carry the single locus genotype associated with elevated levels of the Na-Li countertransport trait had the strongest association with predisposition to hypertension. These associations indicate that predisposition to hypertension cannot be adequately assessed unless Na-Li countertransport genotype is considered. Parental hypertension status also contributed to hypertension prediction. However, once measures of the individual were accounted for, only father's hypertension status information predicted hypertension predisposition in their sons. Therefore, information about an individual's Na-Li countertransport genotype and knowledge of family history of hypertension are valuable predictors of hypertension.