A genome-wide cross-trait analysis identifies causal relationship and shared loci of food preference with obesity

Food preferences play a pivotal role in dietary choices and body weight regulation, yet the causal relationships and complex pathways linking food liking to obesity remain elusive. Here, we employed a two-sample Mendelian randomization (MR) analysis and pleiotropic analysis to explore the causalities and shared loci between 187 food preferences (N=161,625) and five obesity-related phenotypes (N=100,716 to 322,154). MR analysis revealed a causal association between two food-liking phenotypes and increased body mass index (BMI), specifically, onion liking ({beta}, 0.286; 95% CI, 0.185 to 0.387; P = 2.80x10-8), and highly palatable food liking ({beta}, 0.266; 95% CI, 0.140 to 0.391; P = 3.31x10-5). Multivariable MR analysis indicated that the impact of onion liking on BMI persisted even after conditioning on actual onion intake, suggesting a degree of independence in dietary preferences influence. Pleiotropic analysis under a composite null hypothesis detected 32 pleiotropic loci and six colocalized loci in these two trait pairs. Candidate pleiotropic genes associated with onion liking-BMI highlighted biological pathways primarily involved in the sensory perception of smell. These findings enhance our comprehension of the intricate relationship between food preferences and obesity.