Genome-wide linkage analysis of systolic and diastolic blood pressure - The Quebec family study

Background-Blood pressure (BP), an important risk factor for coronary heart disease, is a complex trait with multiple genetic etiologies, While some l oci affecting BP variation are known (eg, angiotensinogen), there are likel y to be novel signals that can be detected with a genome scan approach. Methods and Results-A genome-wide scan was performed in 125 random and 81 o bese families participating in the Quebec Family Study. A multipoint varian ce-components linkage analysis of 420 markers (353 microsatellites and 67 r estriction fragment length polymorphisms) revealed several signals (P<0.002 3) for systolic BP on 1p (D1S551, ATP1A1), 2p (D2S1790, D2S2972), 5p (D5S19 86), 7q (D7S530), 8q (CRH), and 19p (D19S247). Suggestive evidence (0.0023< P<0.01) was found on 3q, 10p, 12p, 14q, and 22q. The results were encouragi ng for HSD3B1 (P<0.03), AGT (P<0.03), ACE (P<0.02), and adipsin (P<0.005) b ut null with regard to other candidates (eg, renin, and glucocorticoid and adrenergic receptors). Conclusions-Multiple linkage regions support the notion that risk for hyper tension is due to multiple (ie, oligogenic) susceptibility loci. Comparison s across the complete, random, and obese samples suggest that some regions are specific to BP and others may involve obesity (eg, pleiotropy, epistasi s, or gene-environment interaction). Some of these areas harbor known candi dates. Others involve novel regions, some of which replicate previous repor ts and provide a focus for future studies to identify novel genes that infl uence interindividual variation in BP.