doi: 10.1161/01.HYP.0000018911.46067.6E
(Hypertension. 2002;39:1037.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Genomewide Linkage Scan of Resting Blood Pressure
HERITAGE Family Study
Division of Biostatistics (T.Ri., M.A.P., D.C.R.) and Departments of Genetics and Psychiatry (D.C.R.), Washington University School of Medicine, St. Louis, Mo; Pennington Biomedical Research Center, Louisiana State University (T.Ra., C.B.), Baton Rouge, La; Genetic and Molecular Psychiatry Unit, Robert-Giffard Research Center (Y.C.C.) and Division of Kinesiology (L.P.), Laval University, Québec, Canada; School of Kinesiology and Leisure Studies, University of Minnesota (A.S.L.), Minneapolis, Minn; Department of Kinesiology, Indiana University (J.S.S.), Bloomington, Ind; and Department of Health and Kinesiology, Texas A&M University (J.H.W.), College Station, Tex.
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
Abstract— The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training–baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families. Linkage evidence (P<0.0023) with baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and 19p12. Results for several known hypertension genes were less compelling. For response BP, results were not very strong, although markers on 13q11 were mildly suggestive (P<0.01). In conclusion, these HERITAGE data, in conjunction with results from previous genomewide scans, provide a basis for planning future investigations. The major areas warranting further study involve fine mapping to narrow down 3 regions on 2q, 3p, and 12q that may contain "novel" hypertension genes, additional typing of some biological candidate genes to determine whether they are the sources of these and other signals, multilocus investigations to understand how and to what extent some of these candidates may interact, and multivariate studies to characterize any pleiotropy.
Key Words: exercise • race • genes • growth substances • receptors, adrenergic • renin-angiotensin system • sodium channels
This article has been cited by other articles:
 |
|
 |
|
  V. A. M. Villar, J. E. Jones, I. Armando, C. Palmes-Saloma, P. Yu, A. M. Pascua, L. Keever, F. B. Arnaldo, Z. Wang, Y. Luo, et al. G Protein-coupled Receptor Kinase 4 (GRK4) Regulates the Phosphorylation and Function of the Dopamine D3 Receptor J. Biol. Chem., August 7, 2009; 284(32): 21425 - 21434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Blizard, A. Lionikas, D. J. Vandenbergh, T. Vasilopoulos, G. S. Gerhard, J. W. Griffith, L. C. Klein, J. T. Stout, H. A. Mack, J. M. Lakoski, et al. Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences Physiol Genomics, February 2, 2009; 36(3): 158 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Shi, C. C. Gu, A. T. Kraja, D. K. Arnett, R. H. Myers, J. S. Pankow, S. C. Hunt, and D. C. Rao Genetic Effect on Blood Pressure Is Modulated by Age: The Hypertension Genetic Epidemiology Network Study Hypertension, January 1, 2009; 53(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Moreno, M. L. Kaldunski, T. Wang, R. J. Roman, A. S. Greene, J. Lazar, H. J. Jacob, and A. W. Cowley Jr. Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat Physiol Genomics, October 19, 2007; 31(2): 228 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Casas, G. L. Cavalleri, L. E. Bautista, L. Smeeth, S. E. Humphries, and A. D. Hingorani Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review Am. J. Epidemiol., November 15, 2006; 164(10): 921 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakayama, N. Kuroi, M. Sano, Y. Tabara, T. Katsuya, T. Ogihara, Y. Makita, A. Hata, M. Yamada, N. Takahashi, et al. Mutation of the Follicle-Stimulating Hormone Receptor Gene 5'-Untranslated Region Associated With Female Hypertension Hypertension, September 1, 2006; 48(3): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Arya, E. Demerath, C. P. Jenkinson, H. H.H. Goring, S. Puppala, V. Farook, S. Fowler, J. Schneider, R. Granato, R. G. Resendez, et al. A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two independent family studies Hum. Mol. Genet., May 15, 2006; 15(10): 1569 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Bell, C. Wallace, R. Dobson, S. Wiltshire, C. Mein, J. Pembroke, M. Brown, D. Clayton, N. Samani, A. Dominiczak, et al. Two-dimensional genome-scan identifies novel epistatic loci for essential hypertension Hum. Mol. Genet., April 15, 2006; 15(8): 1365 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. An, B. I. Freedman, S. S. Rich, S. A. Mandel, D. K. Arnett, R. H. Myers, Y.-D. I. Chen, S. C. Hunt, and D.C. Rao Quantitative Trait Loci on Chromosome 8q24 for Pancreatic {beta}-Cell Function and 7q11 for Insulin Sensitivity in Obese Nondiabetic White and Black Families: Evidence From Genome-Wide Linkage Scans in the NHLBI Hypertension Genetic Epidemiology Network (HyperGEN) Study Diabetes, February 1, 2006; 55(2): 551 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chen, S. Li, S. R Srinivasan, E. Boerwinkle, and G. S. Berenson Autosomal Genome Scan for Loci Linked to Blood Pressure Levels and Trends Since Childhood: The Bogalusa Heart Study Hypertension, May 1, 2005; 45(5): 954 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Lange, T. D. Spector, and T. Andrew Genome-Wide Scan for Blood Pressure Suggests Linkage to Chromosome 11, and Replication of Loci on 16, 17, and 22 Hypertension, December 1, 2004; 44(6): 872 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Koivukoski, S. A. Fisher, T. Kanninen, C. M. Lewis, F. von Wowern, S. Hunt, S. L.R. Kardia, D. Levy, M. Perola, T. Rankinen, et al. Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3 Hum. Mol. Genet., October 1, 2004; 13(19): 2325 - 2332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Pettersson-Fernholm, C. M. Forsblom, M. Perola, J. A. Fagerudd, and P.-H. Groop Dopamine D3 receptor gene polymorphisms, blood pressure and nephropathy in type 1 diabetic patients Nephrol. Dial. Transplant., June 1, 2004; 19(6): 1432 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Mein, M. J. Caulfield, R. J. Dobson, and P. B. Munroe Genetics of essential hypertension Hum. Mol. Genet., April 1, 2004; 13(90001): R169 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. North, K. M. Rose, I. B. Borecki, A. Oberman, S. C. Hunt, M. B. Miller, J. Blangero, L. Almasy, and J. S. Pankow Evidence for a Gene on Chromosome 13 Influencing Postural Systolic Blood Pressure Change and Body Mass Index Hypertension, April 1, 2004; 43(4): 780 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Barkley, A. Chakravarti, R. S. Cooper, R. C. Ellison, S. C. Hunt, M. A. Province, S. T. Turner, A. B. Weder, E. Boerwinkle, and on behalf of the Family Blood Pressure Program Positional Identification of Hypertension Susceptibility Genes on Chromosome 2 Hypertension, February 1, 2004; 43(2): 477 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Forrester Historic and Early Life Origins of Hypertension in Africans J. Nutr., January 1, 2004; 134(1): 211 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. von Wowern, K. Bengtsson, C. M. Lindgren, M. Orho-Melander, F. Fyhrquist, U. Lindblad, L. Rastam, C. Forsblom, T. Kanninen, P. Almgren, et al. A genome wide scan for early onset primary hypertension in Scandinavians Hum. Mol. Genet., August 15, 2003; 12(16): 2077 - 2081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Cowley Jr. Genomics and homeostasis Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R611 - R627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. A. Sonna, S. B. Glueck, and X. Jeunemaitre Exercise, genetics, and blood pressure: Focus on "Physical exercise and blood pressure with reference to the angiotensinogen M235T polymorphism" and on "Angiotensinogen M235T polymorphism associates with exercise hemodynamics in postmenopausal women" Physiol Genomics, August 14, 2002; 10(2): 45 - 47. [Full Text] [PDF]
|
|