Blood pressure QTLs identified by genome-wide linkage analysis and dependence on associated phenotypes

Abstract

Understanding genetic factors that contribute to population-wide variation in blood pressure is likely to benefit prevention and treatment of cardiovascular disease. The aim of the Victorian Family Heart Study is to identify genes for cardiovascular risk in 783 volunteer adult families recruited from the general population. In this preliminary study we sought to identify quantitative trait loci (QTLs) using a genome-wide linkage analysis in 274 adult sibling pairs of average age 24 yr selected without respect to blood pressure. We compared multipoint linkage results for carefully measured systolic (SBP) and diastolic (DBP) pressures before and after statistical adjustment for covariation with sex, oral contraception, age, height, and weight. The average BP was 123/67 (SD: 12/11) mmHg in males ( n = 283) and 114/64 (SD: 10/9) mmHg in females ( n = 265). Nonparametric Z-scores from multipoint GeneHunter II analysis were “suggestive” (3.1 or more) at four QTLs for SBP (chromosomes 1, 4, 16, and X) but at no QTLs for DBP. Most Z-scores were affected little by adjustment for covariates. However, the SBP QTL on chromosome 16 was obvious only for unadjusted pressures. This population-based quantitative trait analysis has identified more QTLs than any of the eight previous genome-wide scans for blood pressure. Considerable discrepancies between different studies may reflect the presence of false-positive results or real biological differences between populations.