TY - JOUR
T1 - Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage
AU - Devan, William J.
AU - Falcone, Guido J.
AU - Anderson, Christopher D.
AU - Jagiella, Jeremiasz M.
AU - Schmidt, Helena
AU - Hansen, Björn M.
AU - Jimenez-Conde, Jordi
AU - Giralt-Steinhauer, Eva
AU - Cuadrado-Godia, Elisa
AU - Soriano, Carolina
AU - Ayres, Alison M.
AU - Schwab, Kristin
AU - Kassis, Sylvia Baedorf
AU - Valant, Valerie
AU - Pera, Joanna
AU - Urbanik, Andrzej
AU - Viswanathan, Anand
AU - Rost, Natalia S.
AU - Goldstein, Joshua N.
AU - Freudenberger, Paul
AU - Stögerer, Eva Maria
AU - Norrving, Bo
AU - Tirschwell, David L.
AU - Selim, Magdy
AU - Brown, Devin L.
AU - Silliman, Scott L.
AU - Worrall, Bradford B.
AU - Meschia, James F.
AU - Kidwell, Chelsea S.
AU - Montaner, Joan
AU - Fernandez-Cadenas, Israel
AU - Delgado, Pilar
AU - Greenberg, Steven M.
AU - Roquer, Jaume
AU - Lindgren, Arne
AU - Slowik, Agnieszka
AU - Schmidt, Reinhold
AU - Woo, Daniel
AU - Rosand, Jonathan
AU - Biffi, Alessandro
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Common genetic variants
KW - Genes
KW - Genetics
KW - Heritability
KW - Intracerebral hemorrhage
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84880149267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880149267&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.111.000089
DO - 10.1161/STROKEAHA.111.000089
M3 - Article
C2 - 23559261
AN - SCOPUS:84880149267
SN - 0039-2499
VL - 44
SP - 1578
EP - 1583
JO - Stroke
JF - Stroke
IS - 6
ER -