Abstract 103: Genetic Markers for Hypertension and Body Mass Index are also Associated with Risk of Intracerebral Hemorrhage

Abstract

Background: Genetic variation plays a substantial role in risk of intracerebral hemorrhage (ICH). Because a number of genetic variants associated with Hypertension (HTN) and Body Mass Index (BMI) have already been identified, and both HTN and BMI influence risk of ICH, we sought to determine whether the cumulative burden of HT and BMI genes increases risk of ICH. Objective: To test the hypothesis that increasing numbers of risk alleles for HTN and high BMI produce additive increments in ICH risk. Methods: Prospective study of consecutive individuals with ICH admitted to the Massachusetts General Hospital between 2004 and 2009, and gender- and age-matched controls. Fourteen SNPs associated with HTN and 42 with high BMI were identified (p-values <5x10E-8) from previous reports and genotyped in our cohort using Illumina 610-QuadBead. Genetic markers unavailable on this platform were imputed. Association analysis for each marker was completed using logistic regression under additive effects model, with gender and age as covariates. The combined effect on ICH of genetic variants for HTN and high BMI was evaluated using a score-based approach. The score for a given individual was calculated as the beta from the regression analysis for each marker, multiplied by the number of risk alleles carried by that subject. The resulting quintile-based score and ICH case-status were the independent and dependent variables, respectively, of a logistic regression model that had gender and age as covariates. Bonferroni-corrected p-values < 0.5/12 = 0.004 were considered significant. Results: A total of 661 subjects were included: 392 cases (186 deep, 194 lobar, 12 multifocal) and 269 controls; mean age 73±9, males 341 (52%). Increasing burdens of risk alleles were associated with increasing risk of ICH in both lobar and deep locations ( Table ). Conclusion: Higher values of a genetic score of HTN and high BMI risk alleles were associated with an increased risk of ICH. This association was more pronounced for deep ICH.