['High alcohol consumption is associated with high IgE levels in observational studies; however, whether high alcohol consumption leads to high IgE levels and allergic disease is unclear.', 'We tested the hypothesis that high alcohol consumption is associated with high IgE levels and allergic disease both observationally and genetically using a Mendelian randomization design free of reverse causation and largely free of confounding.', 'Among 111,408 subjects aged 20 to 100\xa0years from the general population, 50,019 had plasma IgE measurements, and 102,270 were genotyped for the alcohol-metabolizing enzymes alcohol dehydrogenase 1B (ADH-1B; rs1229984) and alcohol dehydrogenase 1c (ADH-1C; rs698). Observationally, we investigated associations between IgE levels and allergic disease (allergic asthma, rhinitis, and eczema) and between alcohol consumption and IgE levels and allergic disease. Genetically, we explored potential causal relationships between alcohol consumption and IgE levels and allergic disease.', 'The multivariable adjusted odds ratio for IgE levels greater than versus less than 150 kU/L and compared with subjects without allergic disease was 2.3 (95% CI, 2.2-2.5) for 1 allergic disease, 3.9 (95% CI, 3.5-4.4) for 2 allergic diseases, and 7.5 (95% CI, 6.2-9.0) for 3 allergic diseases. High alcohol consumption was associated with high IgE levels but not with high risk of allergic disease. The odds ratio for high versus low IgE levels per 1 alcoholic drink per week higher consumption was 1.12 (95% CI, 1.02-1.23) genetically and 1.01 (95% CI, 1.01-1.02) observationally; for allergic disease, the corresponding odds ratios were 0.96 (95% CI, 0.92-1.00) genetically and 1.00 (95% CI, 1.00-1.00) observationally.'] Does high alcohol consumption cause high IgE levels but not high risk of allergic disease?