doi: 10.1161/hs0302.103619
(Stroke. 2002;33:769.)
© 2002 American Heart Association, Inc.
Original Contributions |
Genetic Liability in Stroke
A Long-Term Follow-Up Study of Danish Twins
From Epidemiology, Institute of Public Health (S.B., D.G., A.S., K.C.); Department of Neurology, Odense University Hospital (D.G., S.H.S.), the Danish Twin Register (D.G., A.S., K.C.), and Center for Demographic Research (A.S.), University of Southern Denmark, Odense University, Odense, Denmark.
Correspondence to Søren Bak, Epidemiology, Institute of Public Health, University of Southern Denmark, Main Campus, Odense, Sdr Blvd 23A, 5000 Odense C, Denmark. E-mail SBak{at}health.sdu.dk
Background and Purpose— Few studies have assessed the overall importance of genetic factors on stroke risk, and the results have been contradictory. We used a large, population-based twin register and nationwide registries of death and hospitalization with long-term follow-up to estimate the effect of genetic factors on the risk of stroke.
Methods— Through the population-based Danish Twin Register, we identified same-sex twin pairs born in 1870 through 1952 for whom at least 1 twin was recorded under a stroke diagnosis in the Register of Causes of Death or the Danish National Discharge Register. From the day of the first stroke event in each twin pair, the live co-twins were followed up for stroke. In survival analyses, we estimated the age- and sex-adjusted effect of zygosity on the risk of stroke death or hospitalization for stroke. Concordance rates, tetrachoric correlations, and heritability were also assessed.
Results— Thirty-five of 351 monozygotic pairs (10%) and 34 of 639 dizygotic pairs (5%) were concordant for stroke death. The age- and sex-adjusted relative risk of stroke death in monozygotic compared with dizygotic co-twins was 2.1 (95% CI, 1.3 to 3.3). The probandwise concordance rates were 0.18 (95% CI, 0.14 to 0.22) for monozygotic and 0.10 (95% CI, 0.08 to 0.13) for dizygotic pairs. Thirty-three of 309 monozygotic pairs (11%) and 39 of 560 dizygotic pairs (7%) were concordant for stroke hospitalization or stroke death. The age- and sex-adjusted relative risk of stroke hospitalization or stroke death in monozygotic compared with dizygotic co-twins was 1.5 (95% CI, 0.9 to 2.4). The probandwise concordance rates were 0.19 (95% CI, 0.15 to 0.24) for monozygotic and 0.13 (95% CI, 0.10 to 0.16) for dizygotic pairs. The heritability estimates were 0.32 for the liability to stroke death and 0.17 for the liability to stroke hospitalization or stroke death.
Conclusions— The observed increased risk of stroke death and stroke hospitalization in monozygotic compared with dizygotic co-twins suggests that genetic factors increase the risk of stroke and that the size of this effect is moderate.
Key Words: cerebrovascular disorders • genetics • risk factors • stroke • twins
This article has been cited by other articles:
 |
|
 |
|
  T. Janunger, S. Nilsson-Ardnor, P. -G. Wiklund, P. Lindgren, S. A. Escher, K. Lackovic, A. K. Nilsson, B. Stegmayr, K. Asplund, and D. Holmberg A novel stroke locus identified in a northern Sweden pedigree: Linkage to chromosome 9q31-33 Neurology, November 24, 2009; 73(21): 1767 - 1773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Ikram, S. Seshadri, J. C. Bis, M. Fornage, A. L. DeStefano, Y. S. Aulchenko, S. Debette, T. Lumley, A. R. Folsom, E. G. van den Herik, et al. Genomewide Association Studies of Stroke N. Engl. J. Med., April 23, 2009; 360(17): 1718 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Debette and S. Seshadri Genetics of Atherothrombotic and Lacunar Stroke Circ Cardiovasc Genet, April 1, 2009; 2(2): 191 - 198. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsushita, M. Kubo, K. Yonemoto, T. Ninomiya, K. Ashikawa, B. Liang, J. Hata, Y. Doi, T. Kitazono, S. Ibayashi, et al. Lack of Association Between Variations of PDE4D and Ischemic Stroke in the Japanese Population Stroke, April 1, 2009; 40(4): 1245 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Luke, E. S. O'Meara, C. M. Rowland, D. Shiffman, L. A. Bare, A. R. Arellano, W.T. Longstreth Jr, T. Lumley, K. Rice, R. P. Tracy, et al. Gene Variants Associated With Ischemic Stroke: The Cardiovascular Health Study Stroke, February 1, 2009; 40(2): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Francis, S. Raghunathan, and P. Khanna The role of genetics in stroke Postgrad. Med. J., September 1, 2007; 83(983): 590 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. C. De Geus, N. Kupper, D. I. Boomsma, and H. Snieder Bivariate Genetic Modeling of Cardiovascular Stress Reactivity: Does Stress Uncover Genetic Variance? Psychosom Med, May 1, 2007; 69(4): 356 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. McCaffery, H. Snieder, Y. Dong, and E. de Geus Genetics in Psychosomatic Medicine: Research Designs and Statistical Approaches Psychosom Med, February 1, 2007; 69(2): 206 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nilsson-Ardnor, P.-G. Wiklund, P. Lindgren, A. K. Nilsson, T. Janunger, S. A. Escher, B. Hallbeck, B. Stegmayr, K. Asplund, and D. Holmberg Linkage of Ischemic Stroke to the PDE4D Region on 5q in a Swedish Population Stroke, August 1, 2005; 36(8): 1666 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bevan, L. Porteous, M. Sitzer, and H.S. Markus Phosphodiesterase 4D Gene, Ischemic Stroke, and Asymptomatic Carotid Atherosclerosis Stroke, May 1, 2005; 36(5): 949 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Meschia, T. G. Brott, and R. D. Brown Jr Genetics of Cerebrovascular Disorders Mayo Clin. Proc., January 1, 2005; 80(1): 122 - 132. [Abstract] [PDF]
|
|
|
|
 |
|
 H Markus Genes for stroke J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1229 - 1231. [Full Text] [PDF]
|
|
|
|
|
|
E. Flossmann, U. G.R. Schulz, and P. M. Rothwell Systematic Review of Methods and Results of Studies of the Genetic Epidemiology of Ischemic Stroke Stroke, January 1, 2004; 35(1): 212 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jerrard-Dunne, G. Cloud, A. Hassan, and H. S. Markus Evaluating the Genetic Component of Ischemic Stroke Subtypes: A Family History Study Stroke, June 1, 2003; 34(6): 1364 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Alberts Stroke Genetics Update Stroke, February 1, 2003; 34(2): 342 - 344. [Full Text] [PDF]
|
|