Genome-wide linkage analyses of systolic blood pressure using highly discordant siblings

Background-Elevated blood pressure is a risk factor for cardiovascular, cer ebrovascular, and renal diseases. Complex mechanisms of blood pressure regu lation pose a challenge to identifying genetic factors that influence inter individual blood pressure variation in the population at large. Methods and Results-We performed a genome-wide linkage analysis of systolic blood pressure in humans using an efficient, highly discordant, full-sibli ng design. We identified 4 regions of the human genome that show statistica l significant linkage to genes that influence interindividual systolic bloo d pressure variation (2p22.1 to 2p21, 5q33.3 to 5q34, 6q23.1 to 6q24.1, and 15q25.1 to 15q26.1). These regions contain a number of candidate genes tha t are involved in physiological mechanisms of blood pressure regulation. Conclusions-These results provide both novel information about genome regio ns in humans that influence interindividual blood pressure Variation and a basis for identifying the contributing genes. Identification of the functio nal mutations in these genes may uncover novel mechanisms for blood pressur e regulation and suggest new therapies and prevention strategies.