A Bluher1, W J Devan2,3, E G Holliday4,5, M Nalls6, S Parolo7, S Bione7, A K Giese8, G B Boncoraglio9, J M Maguire10, M Müller-Nurasyid11,12,13, C Gieger14,15, J F Meschia16, J Rosand2,3, A Rolfs8, S J Kittner1,17, B D Mitchell18,19, J R O'Connell18, Y C Cheng18,20. 1. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA. 2. Stroke Service, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 4. Public Health Program, Hunter Medical Research Institute, Newcastle, NSW, Australia. 5. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. 6. Laboratory of Neurogenetics, National Institute of Aging, National Institute of Health, Bethesda, MD, USA. 7. Institute of Molecular Genetics, National Research Council, Pavia, Italy. 8. Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany. 9. Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 10. School of Nursing and Midwifery, University of Newcastle, Newcastle, NSW, Australia. 11. Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 12. Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany. 13. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. 14. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 15. Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 16. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. 17. Department of Neurology, Veterans Affairs Maryland Health Care System, Baltimore, MD, USA. 18. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. 19. Geriatric Research and Education Clinical Center, Veterans Affairs Maryland Health Care System, Baltimore, MD, USA. 20. Research and Development Program, Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
Abstract
BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.
BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.
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