Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage.
Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage.
Available online from MWHC library: 1970 - present, Available in print through MWHC library: 1999 - 2006
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. 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. 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-APOEloci and at 12% (SE, 4%) for APOE.
English
0039-2499
*Cerebral Hemorrhage/di [Diagnosis]
*Cerebral Hemorrhage/ge [Genetics]
*Genetic Predisposition to Disease/ge [Genetics]
*Genetic Variation/ge [Genetics]
*Genome-Wide Association Study
*Severity of Illness Index
Adult
Aged
Aged, 80 and over
Apolipoproteins E/ge [Genetics]
Case-Control Studies
Cerebral Hemorrhage/mo [Mortality]
Female
Genotype
Hematoma/ge [Genetics]
Hematoma/pa [Pathology]
Humans
Male
Middle Aged
Phenotype
Prognosis
Risk Factors
Survival Rate
MedStar Heart & Vascular Institute
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Available online from MWHC library: 1970 - present, Available in print through MWHC library: 1999 - 2006
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. 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. 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-APOEloci and at 12% (SE, 4%) for APOE.
English
0039-2499
*Cerebral Hemorrhage/di [Diagnosis]
*Cerebral Hemorrhage/ge [Genetics]
*Genetic Predisposition to Disease/ge [Genetics]
*Genetic Variation/ge [Genetics]
*Genome-Wide Association Study
*Severity of Illness Index
Adult
Aged
Aged, 80 and over
Apolipoproteins E/ge [Genetics]
Case-Control Studies
Cerebral Hemorrhage/mo [Mortality]
Female
Genotype
Hematoma/ge [Genetics]
Hematoma/pa [Pathology]
Humans
Male
Middle Aged
Phenotype
Prognosis
Risk Factors
Survival Rate
MedStar Heart & Vascular Institute
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't