简介：AbstractObjective:The impact of dairy fat on inflammatory bowel disease remained inconclusive. We aimed to compare the effects of whole-milk and skimmed-milk consumption on the risk of inflammatory bowel disease using a Mendelian randomization analysis.Methods:We conducted a genome-wide association study of the preference for whole versus skimmed milk using data for 20,200 whole-milk consumers and 67,847 skimmed-milk consumers from the UK Biobank. The lead single nucleotide polymorphisms in the associated loci were identified at the genome-wide significance level, and were further employed as instrumental variables for whole-milk preference. We conducted a two-sample Mendelian randomization analysis with whole-milk preference as the exposure and inflammatory bowel disease as the outcome. The pleiotropic effects and heterogeneity of the instrumental variables were estimated using Mendelian randomization-Egger regression and Cochran Q test, respectively. This study was conducted using the UKB resources under the application "53536" . The UK Biobank was approved by the North West Multi-center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland.Results:The genome-wide association study identified five lead nucleotide polymorphisms associated with whole-milk preference. Mendelian randomization indicated that whole-milk preference significantly decreased the risk of inflammatory bowel disease (β=-1.735, P=0.048). Of the two subtypes, whole-milk preference was associated with a lower risk of Crohn disease (β=-2.549, P=0.032), but had no significant effect on the risk of ulcerative colitis (β=-1.002, P=0.44).Conclusion:Consumption of whole-milk fat may protect against Crohn disease, compared with skimmed milk. This conclusion was based on causal inference in a cohort study, and further validation in randomized controlled trials is warranted.