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

ABSTRACT: 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.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.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-APOEloci and at 12% (SE, 4%) for APOE.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.

SUBMITTER: Devan WJ

PROVIDER: S-EPMC3684199 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Devan William J WJ Falcone Guido J GJ Anderson Christopher D CD Jagiella Jeremiasz M JM Schmidt Helena H Hansen Björn M BM Jimenez-Conde Jordi J Giralt-Steinhauer Eva E Cuadrado-Godia Elisa E Soriano Carolina C Ayres Alison M AM Schwab Kristin K Kassis Sylvia Baedorf SB Valant Valerie V Pera Joanna J Urbanik Andrzej A Viswanathan Anand A Rost Natalia S NS Goldstein Joshua N JN Freudenberger Paul P Stögerer Eva-Maria EM Norrving Bo B Tirschwell David L DL Selim Magdy M Brown Devin L DL Silliman Scott L SL Worrall Bradford B BB Meschia James F JF Kidwell Chelsea S CS Montaner Joan J Fernandez-Cadenas Israel I Delgado Pilar P Greenberg Steven M SM Roquer Jaume J Lindgren Arne A Slowik Agnieszka A Schmidt Reinhold R Woo Daniel D Rosand Jonathan J Biffi Alessandro A

Stroke 20130404 6

<h4>Background and purpose</h4>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 ...[more]

PMID: 23559261

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Project description:Background and Purpose- Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre-intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods- Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed "continuous"), and post-ICH only (termed "new"). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results- The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632-1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162-2.408]; P=0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance (P=0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301-0.875]; P=0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions- In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01202864.

Dataset Information

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

Publications

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

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