Prediction of hypertension based on the genetic analysis of longitudinal phenotypes: a comparison of different modeling approaches for the binary trait of hypertension

For the analysis of the longitudinal hypertension family data, we focused on modeling binary traits of hypertension measured repeatedly over time. Our primary objective is to examine predictive abilities of longitudinal models for genetic associations. We first identified single-nucleotide polymorphisms (SNPs) associated with any occurrence of hypertension over the study period to set up covariates for the longitudinal analysis. Then, we proceeded to the longitudinal analysis of the repeated measures of binary hypertension with covariates including SNPs by accounting for correlations arising from repeated outcomes and among family members. We examined two popular models for longitudinal binary outcomes: (a) a marginal model based on the generalized estimating equations, and (b) a conditional model based on the logistic random effect model. The effects of risk factors associated with repeated hypertensions were compared for these two models and their prediction abilities were assessed with and without genetic information. Based on both approaches, we found a significant interaction effect between age and gender where males were at higher risk of hypertension before age 35 years, but after age 35 years, women were at higher risk. Moreover, the SNPs were significantly associated with hypertension after adjusting for age, gender, and smoking status. The SNPs contributed more to predict hypertension in the marginal model than in the conditional model. There was substantial correlation among repeated measures of hypertension, implying that hypertension was considerably correlated with previous experience of hypertension. The conditional model performed better for predicting the future hypertension status of individuals.