(Circulation. 2000;102:1956.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Genome-Wide Linkage Analysis of Systolic and Diastolic Blood Pressure
The Québec Family Study
From the Division of Biostatistics (T. Rice, M.A.P., I.B.B., D.C.R.) and Departments of Genetics (I.B.B., D.C.R.) and Psychiatry (D.C.R.), Washington University School of Medicine, St Louis, Mo; Physical Activity Sciences Laboratory, Laval University, Québec, Canada (Y.C.C., L.P.); and Pennington Biomedical Research Center, Baton Rouge, La (T. Rankinen, C.B.).
Correspondence to Treva Rice, PhD, Division of Biostatistics, Washington University School of Medicine, Box 8067, 660 S Euclid Ave, St Louis, MO 63110. E-mail treva{at}wubios.wustl.edu
Background—Blood pressure (BP), an important risk factor for coronary heart disease, is a complex trait with multiple genetic etiologies. While some loci affecting BP variation are known (eg, angiotensinogen), there are likely 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 obese families participating in the Québec Family Study. A multipoint variance-components linkage analysis of 420 markers (353 microsatellites and 67 restriction fragment length polymorphisms) revealed several signals (P<0.0023) for systolic BP on 1p (D1S551, ATP1A1), 2p (D2S1790, D2S2972), 5p (D5S1986), 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 encouraging for HSD3B1 (P<0.03), AGT (P<0.03), ACE (P<0.02), and adipsin (P<0.005) but null with regard to other candidates (eg, renin, and glucocorticoid and adrenergic receptors).
Conclusions—Multiple linkage regions support the notion that risk for hypertension is due to multiple (ie, oligogenic) susceptibility loci. Comparisons across the complete, random, and obese samples suggest that some regions are specific to BP and others may involve obesity (eg, pleiotropy, epistasis, or gene-environment interaction). Some of these areas harbor known candidates. Others involve novel regions, some of which replicate previous reports and provide a focus for future studies to identify novel genes that influence interindividual variation in BP.
Key Words: hypertension • blood pressure • genetics • coronary disease
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