Causal relationship between dairy intake and obesity: A 2-sample bidirectional and multivariable Mendelian randomization study.

This study aimed to investigate the causal relationship between intake of specific milk and dairy products (whole, semiskimmed, and skim milk; cream; ice cream; yogurt; and cheese) and obesity due to excess calories using genetic instruments. A 2-sample bidirectional Mendelian randomization (MR) study was conducted using summary-level data from large-scale genome-wide association studies. Genetic variants associated with dairy intake and obesity were used as instrumental variables. The primary analysis used the inverse variance weighted (IVW) method, supplemented by sensitivity analyses to test for pleiotropy and heterogeneity. Multivariable MR (MVMR) was subsequently applied to estimate the independent effect of significant exposures, adjusting for key confounders. In univariate MR analyses, genetic predisposition to higher cheese intake was associated with a lower risk of obesity (IVW: odds ratio [OR] = 0.37, 95% CI: 0.15-0.91). No significant causal effects were found for other dairy products, and reverse MR analyses indicated no effect of obesity on dairy intake. Sensitivity analyses supported the robustness of these findings. Crucially, in MVMR analysis adjusting for confounding factors, only cheese intake retained a significant inverse association with obesity (IVW: OR = 0.30, 95% CI: 0.12-0.74), indicating an independent inverse causal association. This MR study provides genetic evidence that cheese intake may have an independent, causal role in reducing the risk of obesity due to excess calories. These findings highlight the importance of distinguishing between different types of dairy products in nutritional epidemiological research and suggest that cheese, as a food with relatively high nutrient density, warrants further investigation regarding its potential role in obesity prevention.