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, Stella 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

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1578-1583
Number of pages6
JournalStroke
Volume44
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Cerebral Hemorrhage
Apolipoproteins E
Hematoma
Genome
Apolipoprotein E4
Phenotype
Mortality
Pedigree
Genotype

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Devan, W. J., Falcone, G. J., Anderson, C. D., Jagiella, J. M., Schmidt, H., Hansen, B. M., ... Biffi, A. (2013). Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. Stroke, 44(6), 1578-1583. https://doi.org/10.1161/STROKEAHA.111.000089

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

In: Stroke, Vol. 44, No. 6, 06.2013, p. 1578-1583.

Research output: Contribution to journalArticle

Devan, WJ, Falcone, GJ, Anderson, CD, Jagiella, JM, Schmidt, H, Hansen, BM, Jimenez-Conde, J, Giralt-Steinhauer, E, Cuadrado-Godia, E, Soriano, C, Ayres, AM, Schwab, K, Kassis, SB, Valant, V, Pera, J, Urbanik, A, Viswanathan, A, Rost, NS, Goldstein, JN, Freudenberger, P, Stögerer, EM, Norrving, B, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, S, Montaner, J, Fernandez-Cadenas, I, Delgado, P, Greenberg, SM, Roquer, J, Lindgren, A, Slowik, A, Schmidt, R, Woo, D, Rosand, J & Biffi, A 2013, 'Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage', Stroke, vol. 44, no. 6, pp. 1578-1583. https://doi.org/10.1161/STROKEAHA.111.000089
Devan, William J. ; Falcone, Guido J. ; Anderson, Christopher D. ; Jagiella, Jeremiasz M. ; Schmidt, Helena ; Hansen, Björn M. ; Jimenez-Conde, Jordi ; Giralt-Steinhauer, Eva ; Cuadrado-Godia, Elisa ; Soriano, Carolina ; Ayres, Alison M. ; Schwab, Kristin ; Kassis, Sylvia Baedorf ; Valant, Valerie ; Pera, Joanna ; Urbanik, Andrzej ; Viswanathan, Anand ; Rost, Natalia S. ; Goldstein, Joshua N. ; Freudenberger, Paul ; Stögerer, Eva Maria ; Norrving, Bo ; Tirschwell, David L. ; Selim, Magdy ; Brown, Devin L. ; Silliman, Scott L. ; Worrall, Bradford B. ; Meschia, James F. ; Kidwell, Stella ; Montaner, Joan ; Fernandez-Cadenas, Israel ; Delgado, Pilar ; Greenberg, Steven M. ; Roquer, Jaume ; Lindgren, Arne ; Slowik, Agnieszka ; Schmidt, Reinhold ; Woo, Daniel ; Rosand, Jonathan ; Biffi, Alessandro. / Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. In: Stroke. 2013 ; Vol. 44, No. 6. pp. 1578-1583.
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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.",
keywords = "Common genetic variants, Genes, Genetics, Heritability, Intracerebral hemorrhage, Stroke",
author = "Devan, {William J.} and Falcone, {Guido J.} and Anderson, {Christopher D.} and Jagiella, {Jeremiasz M.} and Helena Schmidt and Hansen, {Bj{\"o}rn M.} and Jordi Jimenez-Conde and Eva Giralt-Steinhauer and Elisa Cuadrado-Godia and Carolina Soriano and Ayres, {Alison M.} and Kristin Schwab and Kassis, {Sylvia Baedorf} and Valerie Valant and Joanna Pera and Andrzej Urbanik and Anand Viswanathan and Rost, {Natalia S.} and Goldstein, {Joshua N.} and Paul Freudenberger and St{\"o}gerer, {Eva Maria} and Bo Norrving and Tirschwell, {David L.} and Magdy Selim and Brown, {Devin L.} and Silliman, {Scott L.} and Worrall, {Bradford B.} and Meschia, {James F.} and Stella Kidwell and Joan Montaner and Israel Fernandez-Cadenas and Pilar Delgado and Greenberg, {Steven M.} and Jaume Roquer and Arne Lindgren and Agnieszka Slowik and Reinhold Schmidt and Daniel Woo and Jonathan Rosand and Alessandro Biffi",
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language = "English (US)",
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journal = "Stroke",
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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, Stella

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

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U2 - 10.1161/STROKEAHA.111.000089

DO - 10.1161/STROKEAHA.111.000089

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JO - Stroke

JF - Stroke

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