Results:

Mean age was 52 years (standard deviation, 11 years), 33% of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% of women with wide variation among study areas. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischemic stroke, intracerebral hemorrhage, and MI; men who reported drinking about 100 g of alcohol per week (1-2 drinks per day) had lower risks of all three diseases than nondrinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week, i.e., near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral hemorrhage (RR per 280 g per week, 1.58; p < 0.0001) than for ischemic stroke (1.27; p = 0.0001). For MI, however, genotype-predicted mean alcohol intake was not significantly associated with risk. Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p < 0.0001). Among women, few drank, and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or MI.