Health effects of milk consumption: phenome-wide Mendelian randomization study

Abstract Background We performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population. Methods Rs4988235 located upstream of the LCT gene was used as the instrumental variable for milk consumption. MR-PheWAS analysis was conducted to map the association of genetically predicted milk consumption with 1081 phenotypes in the UK Biobank study ( n =339,197). The associations identified in MR-PheWAS were examined by two-sample MR analysis using data from the FinnGen study ( n =260,405) and international consortia. A systematic review of MR studies on milk consumption was further performed. Results PheWAS and two-sample MR analyses found robust evidence in support of inverse associations of genetically predicted milk consumption with risk of cataract (odds ratio (OR) per 50 g/day increase in milk consumption, 0.89, 95% confidence interval (CI), 0.84–0.94; p =3.81×10 −5 ), hypercholesterolemia (OR, 0.91, 95% CI 0.86–0.96; p =2.97×10 −4 ), and anal and rectal polyps (OR, 0.85, 95% CI, 0.77–0.94; p =0.001). An inverse association for type 2 diabetes risk (OR, 0.92, 95% CI, 0.86–0.97; p =0.003) was observed in MR analysis based on genetic data with body mass index adjustment but not in the corresponding data without body mass index adjustment. The systematic review additionally found evidence that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer’s disease, and positively associated with Parkinson’s disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity. Conclusions This study suggests several health effects of milk consumption in the European population.