Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.

ABSTRACT: OBJECTIVE:Prior studies investigating the association between APOE alleles ?2/?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 ?2 and ?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 ?2 and ?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 × 10(-10); and OR = 2.20, 95%CI = 1.85-2.63, p = 2.4 × 10(-11), respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele ?4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08-1.36, p = 2.6 × 10(-4)). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. INTERPRETATION:APOE ?2 and ?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 ?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.

SUBMITTER: Biffi A 

PROVIDER: S-EPMC3058266 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature