(Hypertension. 2000;36:477.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Evidence for a Gene Influencing Blood Pressure on Chromosome 17
Genome Scan Linkage Results for Longitudinal Blood Pressure Phenotypes in Subjects From the Framingham Heart Study
From the National Heart, Lung, and Blood Institute Framingham Heart Study (D.L., M.G.L., C.J.D.), Framingham, Mass; the Department of Epidemiology and Biostatistics (A.L.D.S., L.A.C.), Boston University School of Public Health, Boston, Mass; the Department of Neurology (A.L.D.S., M.G.L., R.H.M.), the Cardiology Division (D.L.), the Genetics Program (A.L.D.S.), and the Hypertension Section (H.G.), Department of Medicine, Boston University School of Medicine, Boston, Mass; the Cardiology Division (C.J.D.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass; and the Howard Hughes Medical Institute (R.P.L.), Departments of Genetics and Medicine, Yale University School of Medicine, New Haven, Conn.
Abstract—Hypertension is a leading cause of morbidity and mortality. Efforts to identify hypertension genes have focused on 3 approaches: mendelian disorders, candidate genes, and genome-wide scans. Thus far, these efforts have not identified genes that contribute substantively to overall blood pressure (BP) variation in the community. A 10-centiMorgan (cM) density genome-wide scan was performed in the largest families from 2 generations of Framingham Heart Study participants. Heritability and linkage for long-term mean systolic and diastolic BP phenotypes were analyzed by use of SOLAR software. Heritability estimates were based on BP measurements in 1593 families. Genotyping was performed on 1702 subjects from 332 large families, and BP data were available for 1585 (93%) genotyped subjects who contributed 12 588 longitudinal BP observations. The mean age was 47 years, and mean BP was 127/80 (systolic/diastolic) mm Hg. Long-term systolic and diastolic BP phenotypes had high heritability estimates, 0.57 and 0.56, respectively. For systolic BP, multipoint log-of-the-odds (LOD) scores >2.0 were located on chromosome 17 at 67 cM (LOD 4.7, P=0.0000016) and 94 cM (LOD 2.2). For diastolic BP, LOD scores >2.0 were identified on chromosome 17 (74 cM, LOD 2.1) and chromosome 18 (7 cM, LOD 2.1). Using a genome-wide scan, we found strong evidence for a BP quantitative trait locus on chromosome 17. Follow-up studies are warranted to identify the gene or genes in this quantitative trait locus that influence BP. Such knowledge could extend our understanding of the genetic basis of essential hypertension and have implications for the evaluation and treatment of patients with high BP.
Key Words: genetics • genome scan • linkage • epidemiology • hypertension, essential • blood pressure • Framingham Heart Study
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P. M. Erlich, J. Cui, I. Chazaro, L. A. Farrer, C. T. Baldwin, H. Gavras, and A. L. DeStefano Genetic Variants of WNK4 in Whites and African Americans With Hypertension Hypertension, June 1, 2003; 41(6): 1191 - 1195. [Abstract] [Full Text] [PDF]
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X. Zhu, Y.-P. C. Chang, D. Yan, A. Weder, R. Cooper, A. Luke, D. Kan, and A. Chakravarti Associations Between Hypertension and Genes in the Renin-Angiotensin System Hypertension, May 1, 2003; 41(5): 1027 - 1034. [Abstract] [Full Text] [PDF]
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Y. Y. Fadl, W. Zareba, A. J. Moss, V. J. Marder, C. S. Sparks, L. F. Miller Watelet, and E. R. Carroll History of Hypertension and Enhanced Thrombogenic Activity in Postinfarction Patients Hypertension, April 1, 2003; 41(4): 943 - 949. [Abstract] [Full Text] [PDF]
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J. Monti, H. Zimdahl, H. Schulz, R. Plehm, D. Ganten, and N. Hubner The Role of Wnk4 in Polygenic Hypertension: A Candidate Gene Analysis on Rat Chromosome 10 Hypertension, April 1, 2003; 41(4): 938 - 942. [Abstract] [Full Text] [PDF]
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C. S. Fox, J. F. Polak, I. Chazaro, A. Cupples, P. A. Wolf, R. A. D'Agostino, and C. J. O'Donnell Genetic and Environmental Contributions to Atherosclerosis Phenotypes in Men and Women: Heritability of Carotid Intima-Media Thickness in the Framingham Heart Study Stroke, February 1, 2003; 34(2): 397 - 401. [Abstract] [Full Text] [PDF]
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J. S. Cui, J. L. Hopper, and S. B. Harrap Antihypertensive Treatments Obscure Familial Contributions to Blood Pressure Variation Hypertension, February 1, 2003; 41(2): 207 - 210. [Abstract] [Full Text] [PDF]
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 D. Gordon, M. B. Corwin, C. S. Mellersh, E. A. Ostrander, and J. Ott Establishing Appropriate Genome-Wide Significance Levels for Canine Linkage Analyses J. Hered., January 1, 2003; 94(1): 1 - 7. [Abstract] [Full Text] [PDF]
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G. Engstrom, L. Janzon, G. Berglund, P. Lind, L. Stavenow, B. Hedblad, and F. Lindgarde Blood Pressure Increase and Incidence of Hypertension in Relation to Inflammation-Sensitive Plasma Proteins Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2054 - 2058. [Abstract] [Full Text] [PDF]
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C. Barlassina, C. Lanzani, P. Manunta, and G. Bianchi Genetics of Essential Hypertension: From Families to Genes J. Am. Soc. Nephrol., November 1, 2002; 13(90003): S155 - 164. [Abstract] [Full Text]
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R. S. Cooper, A. Luke, X. Zhu, D. Kan, A. Adeyemo, C. Rorimi, N. Bouzekri, and R. Ward Genome Scan Among Nigerians Linking Blood Pressure to Chromosomes 2, 3, and 19 Hypertension, November 1, 2002; 40(5): 629 - 633. [Abstract] [Full Text] [PDF]
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T. A. Kotchen, U. Broeckel, C. E. Grim, P. Hamet, H. Jacob, M. L. Kaldunski, J. M. Kotchen, N. J. Schork, P. J. Tonellato, and A. W. Cowley Jr Identification of Hypertension-Related QTLs in African American Sib Pairs Hypertension, November 1, 2002; 40(5): 634 - 639. [Abstract] [Full Text] [PDF]
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M. Tomaszewski, N. J.R. Brain, F. J. Charchar, W. Y.S. Wang, B. Lacka, S. Padmanabahn, J. S. Clark, N. H. Anderson, H. V. Edwards, E. Zukowska-Szczechowska, et al. Essential Hypertension and {beta}2-Adrenergic Receptor Gene: Linkage and Association Analysis Hypertension, September 1, 2002; 40(3): 286 - 291. [Abstract] [Full Text] [PDF]
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S. C. Hunt, R. C. Ellison, L. D. Atwood, J. S. Pankow, M. A. Province, and M. F. Leppert Genome Scans for Blood Pressure and Hypertension: The National Heart, Lung, and Blood Institute Family Heart Study Hypertension, July 1, 2002; 40(1): 1 - 6. [Abstract] [Full Text] [PDF]
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K. Kristjansson, A. Manolescu, A. Kristinsson, T. Hardarson, H. Knudsen, S. Ingason, G. Thorleifsson, M. L. Frigge, A. Kong, J. R. Gulcher, et al. Linkage of Essential Hypertension to Chromosome 18q Hypertension, June 1, 2002; 39(6): 1044 - 1049. [Abstract] [Full Text] [PDF]
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H. Zimdahl, T. Kreitler, C. Gosele, D. Ganten, and N. Hubner Conserved Synteny in Rat and Mouse for a Blood Pressure QTL on Human Chromosome 17 Hypertension, June 1, 2002; 39(6): 1050 - 1052. [Abstract] [Full Text] [PDF]
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 B. Swynghedauw Susceptibility-conferring polymorphic genotypes in cardiovascular multifactorial syndromes Eur. Heart J., February 2, 2002; 23(4): 271 - 273. [Full Text] [PDF]
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P. A. Doris Hypertension Genetics, Single Nucleotide Polymorphisms, and the Common Disease:Common Variant Hypothesis Hypertension, February 1, 2002; 39(2): 323 - 331. [Abstract] [Full Text] [PDF]
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 S-Y Wu, C S J Fann, Y-S Jou, J-W Chen, and W-H Pan Association between markers in chromosomal region 17q23 and young onset hypertension: a TDT study J. Med. Genet., January 1, 2002; 39(1): 42 - 44. [Full Text] [PDF]
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S. Francke, M. Manraj, C. Lacquemant, C. Lecoeur, F. Lepretre, P. Passa, A. Hebe, L. Corset, S. L. K. Yan, S. Lahmidi, et al. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27 Hum. Mol. Genet., November 1, 2001; 10(24): 2751 - 2765. [Abstract] [Full Text] [PDF]
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M. R. Garrett, X. Zhang, O. I. Dukhanina, A. Y. Deng, and J. P. Rapp Two Linked Blood Pressure Quantitative Trait Loci on Chromosome 10 Defined by Dahl Rat Congenic Strains Hypertension, October 1, 2001; 38(4): 779 - 785. [Abstract] [Full Text] [PDF]
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 F. H. Wilson, S. Disse-Nicodeme, K. A. Choate, K. Ishikawa, C. Nelson-Williams, I. Desitter, M. Gunel, D. V. Milford, G. W. Lipkin, J.-M. Achard, et al. Human Hypertension Caused by Mutations in WNK Kinases Science, August 10, 2001; 293(5532): 1107 - 1112. [Abstract] [Full Text] [PDF]
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 S. B. Harrap and S. Petrou Utility of genetic approaches to common cardiovascular diseases Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H1 - H6. [Full Text] [PDF]
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T. Rankinen, P. An, T. Rice, G. Sun, Y. C. Chagnon, J. Gagnon, A. S. Leon, J. S. Skinner, J. H. Wilmore, D. C. Rao, et al. Genomic Scan for Exercise Blood Pressure in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study Hypertension, July 1, 2001; 38(1): 30 - 37. [Abstract] [Full Text] [PDF]
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F. C. Luft and A. Busjahn Peaks and Valleys Hypertension, July 1, 2001; 38(1): 38 - 40. [Full Text] [PDF]
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 N. Padmanabhan, S. Padmanabhan, and J. M. Connell Genetic basis of cardiovascular disease -- the renin-angiotensin-aldosterone system as a paradigm Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 316 - 324. [PDF]
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R. N. Re On the Sequencing of the Human Genome Hypertension, October 1, 2000; 36(4): 469 - 470. [Full Text] [PDF]
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S. B. HARRAP, Z. Y. H. WONG, M. STEBBING, A. LAMANTIA, and M. BAHLO Blood pressure QTLs identified by genome-wide linkage analysis and dependence on associated phenotypes Physiol Genomics, February 28, 2002; 8(2): 99 - 105. [Abstract] [Full Text] [PDF]
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