Multipoint association mapping for longitudinal family data: an application to hypertension phenotypes

It is essential to develop adequate statistical methods to fully utilize information from longitudinal family studies. We extend our previous multipoint linkage disequilibrium approach—simultaneously accounting for correlations between markers and repeat measurements within subjects, and the correlations between subjects in families—to detect loci relevant to disease through gene-based analysis. Estimates of disease loci and their genetic effects along with their 95 % confidence intervals (or significance levels) are reported. Four different phenotypes—ever having hypertension at 4 visits, incidence of hypertension, hypertension status at baseline only, and hypertension status at 4 visits—are studied using the proposed approach. The efficiency of estimates of disease locus positions (inverse of standard error) improves when using the phenotypes from 4 visits rather than using baseline only.