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Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage

Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn LU ; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa and Soriano, Carolina, et al. (2013) In Stroke: a journal of cerebral circulation 44(6). p.1578-1583
Abstract
Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured... (More)
Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE. Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified. (Less)
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published
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keywords
common genetic variants, genetics, genes, heritability, intracerebral, hemorrhage, stroke
in
Stroke: a journal of cerebral circulation
volume
44
issue
6
pages
1578 - 1583
publisher
American Heart Association
external identifiers
  • wos:000319465400022
  • scopus:84880149267
ISSN
1524-4628
DOI
10.1161/STROKEAHA.111.000089
language
English
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yes
id
4dcf7be7-d7a2-4dba-949c-e7d254528f32 (old id 3931050)
date added to LUP
2013-08-01 07:37:52
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2019-03-19 02:19:26
@article{4dcf7be7-d7a2-4dba-949c-e7d254528f32,
  abstract     = {Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE. Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.},
  author       = {Devan, William J. and Falcone, Guido J. and Anderson, Christopher D. and Jagiella, Jeremiasz M. and Schmidt, Helena and Hansen, Björn and Jimenez-Conde, Jordi and Giralt-Steinhauer, Eva and Cuadrado-Godia, Elisa and Soriano, Carolina and Ayres, Alison M. and Schwab, Kristin and Kassis, Sylvia Baedorf and Valant, Valerie and Pera, Joanna and Urbanik, Andrzej and Viswanathan, Anand and Rost, Natalia S. and Goldstein, Joshua N. and Freudenberger, Paul and Stoegerer, Eva-Maria and Norrving, Bo and Tirschwell, David L. and Selim, Magdy and Brown, Devin L. and Silliman, Scott L. and Worrall, Bradford B. and Meschia, James F. and Kidwell, Chelsea S. and Montaner, Joan and Fernandez-Cadenas, Israel and Delgado, Pilar and Greenberg, Steven M. and Roquer, Jaume and Lindgren, Arne and Slowik, Agnieszka and Schmidt, Reinhold and Woo, Daniel and Rosand, Jonathan and Biffi, Alessandro},
  issn         = {1524-4628},
  keyword      = {common genetic variants,genetics,genes,heritability,intracerebral,hemorrhage,stroke},
  language     = {eng},
  number       = {6},
  pages        = {1578--1583},
  publisher    = {American Heart Association},
  series       = { Stroke: a journal of cerebral circulation},
  title        = {Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.111.000089},
  volume       = {44},
  year         = {2013},
}