Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Biffi, A; Sonni, A; Anderson, CD; Kissela, B; Jagiella, JM; Schmidt, H; Jimenez-Conde, J; Hansen, BM; Fernandez-Cadenas, I; Cortellini, L; Ayres, A; Schwab, K; Juchniewicz, K; Urbanik, A; Rost, NS; Viswanathan, A; Seifert-Held, T; Stoegerer, EM; Tomás, M; Rabionet, R; Estivill, X; Brown, DL; Silliman, SL; Selim, M; Worrall, BB; Meschia, JF; Montaner, J; Lindgren, A; Roquer, J; Schmidt, R; Greenberg, SM; Slowik, A; Broderick, JP; Woo, D; Rosand, J; on behalf of the International Stroke Genetics Consortium.
Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.
Ann Neurol. 2010; 68(6): 934-943.
Doi: 10.1002/ana.22134
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- Co-Autor*innen der Med Uni Graz
- Schmidt Helena
- Schmidt Reinhold
- Seifert-Held Thomas
- Stögerer-Oberschmid Eva Maria
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- Abstract:
- Objective: Prior studies investigating the association between APOE alleles epsilon 2/epsilon 4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied. Methods: We performed a large-scale genetic association study of 2189 ICH cases and 4041 controls from 7 cohorts, which were analyzed using additive models for epsilon 2 and epsilon 4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases, 357 controls) had available genome-wide data to adjust for population stratification. Results: Alleles epsilon 2 and epsilon 4 were associated with lobar ICH at genome-wide significance levels (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.50-2.23, p = 6.6 x 10(-10); and OR = 2.20, 95%CI = 1.85-2.63, p = 2.4 x 10(-11), respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele epsilon 4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08-1.36, p = 2.6 x 10(-4)). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. Interpretation: APOE epsilon 2 and epsilon 4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE epsilon 4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied. ANN NEUROL 2010;68:934-943
- Find related publications in this database (using NLM MeSH Indexing)
- African Americans -
- Aged -
- Aged, 80 and over -
- Apolipoprotein E2 - genetics
- Apolipoprotein E4 - genetics
- Cerebral Amyloid Angiopathy -
- Cerebral Hemorrhage - epidemiology Cerebral Hemorrhage - genetics Cerebral Hemorrhage - radiography
- Cohort Studies -
- Cross-Cultural Comparison -
- European Continental Ancestry Group -
- Female -
- Gene Frequency -
- Genetic Predisposition to Disease -
- Genetic Variation - genetics
- Genome-Wide Association Study -
- Genotype -
- Humans -
- Male -
- Meta-Analysis as Topic -
- Middle Aged -
- Models, Genetic -
- Principal Component Analysis -
- Risk Factors -