The primary goal of this application is to determine the important genetic and environmental risk factors for intracerebral hemorrhage (ICH) and Subarachnoid hemorrhage (SAH), which occur in over 50,000 Americans each year and yield a combined mortality of 40- 50% all cases of ICH and SAH in a racially mixed metropolitan population of 1.3 million (14% African-American) will be identified over 3 years. Two age-, gender, and race matched controls will be identified for each case by random-digit-dialing (RDD). A study nurse will perform a 1-hour interview of cases and controls including blood pressure measurements and buccal swabs for genetic testing. Data from 470 cases of ICH, 250 cases of SAH, 720 case proxies, 1440 controls, and 360 control proxies will be used to test the following hypotheses: Hypothesis 1: the ApoE4 and ApoE2 alleles are significant and independent risk factors for lobar hemorrhage in persons over the age of 50. The presence of an ApoE4 or ApoE2 allele is not significant risk factor for ganglionic or deep white matter hemorrhages. Hypothesis 2: Age, hypertension, prior cerebral infarction, current smoking, use of anticoagulants, heavy alcohol use, diabetes, and the presence of an ApoE4 or ApoE2 allele are significant and independent risk factors for ICH. Hypertension will be the modifiable risk factor with the greatest attributable risk. Hypothesis 3: the presence of a Z or S mutation of the normal M1 allele for alpha-1 antitrypsin is associated with an increased risk of aneurysmal SAH. Hypothesis 4: Age, female gender, cigarette smoking, hypertension, estrogen deficiency among women, a family history of SAH, and the presence of Z or S mutation of the normal M1 allele for alpha-1 antitrypsin are significant risk factors for SAH. Smoking will be the modifiable risk factors with the greatest attributable risk. Hypothesis 5: although the age- and sex-adjusted incidence rates of both ICH and SAH will be increased among African-Americans as compared to whites, race will not be an independent risk factor for either ICH or SAH.
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