Comparison of univariate and multivariate linkage analysis of traits related to hypertension

Complex traits are often manifested by multiple correlated traits. One example of this is hypertension (HTN), which is measured on a continuous scale by systolic blood pressure (SBP). Predisposition to HTN is predicted by hyperlipidemia, characterized by elevated triglycerides (TG), low-density lipids (LDL), and high-density lipids (HDL). We hypothesized that the multivariate analysis of TG, LDL, and HDL would be more powerful for detecting HTN genes via linkage analysis compared with univariate analysis of SBP. We conducted linkage analysis of four chromosomal regions known to contain genes associated with HTN using SBP as a measure of HTN in univariate Haseman-Elston regression and using the correlated traits TG, LDL, and HDL in multivariate Haseman-Elston regression. All analyses were conducted using the Framingham Heart Study data. We found that multivariate linkage analysis was better able to detect chromosomal regions in which the angiotensinogen, angiotensin receptor, guanine nucleotide-binding protein 3, and prostaglandin I2 synthase genes reside. Univariate linkage analysis only detected the AGT gene. We conclude that multivariate analysis is appropriate for the analysis of multiple correlated phenotypes, and our findings suggest that it may yield new linkage signals undetected by univariate analysis.