Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage

William J. Devan, Guido J. Falcone, Christopher D. Anderson, Jeremiasz M. Jagiella, Helena Schmidt, Björn M. Hansen, Jordi Jimenez-Conde, Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, Carolina Soriano, Alison M. Ayres, Kristin Schwab, Sylvia Baedorf Kassis, Valerie Valant, Joanna Pera, Andrzej Urbanik, Anand Viswanathan, Natalia S. Rost, Joshua N. Goldstein, Paul FreudenbergerEva Maria Stögerer, Bo Norrving, David L. Tirschwell, Magdy Selim, Devin L. Brown, Scott L. Silliman, Bradford B. Worrall, James F. Meschia, Chelsea S. Kidwell, Joan Montaner, Israel Fernandez-Cadenas, Pilar Delgado, Steven M. Greenberg, Jaume Roquer, Arne Lindgren, Agnieszka Slowik, Reinhold Schmidt, Daniel Woo, Jonathan Rosand, Alessandro Biffi

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    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. © 2013 American Heart Association, Inc.
    Original languageEnglish
    Pages (from-to)1578-1583
    JournalStroke
    Volume44
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2013

    Keywords

    • Common genetic variants
    • Genes
    • Genetics
    • Heritability
    • Intracerebral hemorrhage
    • Stroke

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