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.