Each box represents HR with the area inversely proportional to the variance of the group-specific log hazard within subplot. The vertical lines indicate group-specific 95% CIs. Conventional epidemiological analyses relate self-reported drinking patterns to risks of diseases (reference group is occasional drinkers), using Cox models stratified by age at risk and study area and adjusted for education and smoking. Within current drinkers, HRs were plotted against usual alcohol intake and were calculated per 280 g per week higher usual alcohol intake. Genetic epidemiological analyses relate genetic categories to risks of diseases (reference group is the genotype group with lowest genotype-predicted mean male alcohol intake), using Cox models stratified by age at risk and study area and adjusted for genomic principal components. The HR per 280 g per week higher genotype-predicted mean male alcohol intake was calculated from the inverse-variance-weighted mean of the slopes of the fitted lines in each study area. The corresponding slopes in women were summarized in text and the slopes of the fitted line by sex were compared and assessed for heterogeneity using chi-squared tests (indicated by P for heterogeneity by sex). All P values are two-sided. Analyses of these aggregated outcomes were based on first recorded event of the aggregate during follow-up and participants may have had multiple events of different types of diseases. All alcohol-related diseases includes the first recorded event from CKB WHO alcohol-related diseases or CKB new alcohol-associated diseases during follow-up.
