Ultra-processed food intake, genetic polymorphisms, and the risk of obesity in a pooled analysis of three prospective cohorts

Obesity is a major risk factor for non-communicable diseases and mortality. This study aimed to examine the associations between ultra-processed food intake and the risks of obesity and weight gain, and to evaluate whether these associations differed by polygenic scores for obesity in Korean adults. This prospective cohort study included 77,344 Korean adults aged 40 years and older from the Health Examinees (HEXA), the Cardiovascular Disease Association Study (CAVAS), and the Korea Association Resource (KARE). Dietary intake was assessed using a food frequency questionnaire, and ultra-processed foods were classified based on the Nova system. Polygenic scores linked to obesity were computed from 27 single nucleotide polymorphisms. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Over median follow-up periods of 4.25, 8.34, and 15.75 years in HEXA, CAVAS, and KARE, respectively, a total of 4,674 (9.15%) participants developed obesity defined as body mass index ≥ 25 kg/m 2 according to the Asia-Pacific criteria, and 3,709 (4.80%) experienced annual weight gain ≥ 1 kg. Compared with the lowest quintile of ultra-processed food intake, the pooled OR (95% CI) for incident obesity was 1.25 (1.11, 1.39) in the highest quintile ( p for trend < 0.001). The pooled ORs (95% CIs) comparing the extreme quartiles of ultra-processed food intake were 1.15 (1.01, 1.32; p for trend = 0.016) and 1.36 (1.15, 1.60; p for trend < 0.001) for metabolically healthy and unhealthy obesity, respectively. For weight gain, the OR (95% CI) was 1.22 (1.09, 1.37) in the highest versus the lowest quintile ( p for trend < 0.001). Associations did not vary by polygenic scores (all p for interaction > 0.10). Higher ultra-processed food intake was associated with increased risks of obesity and weight gain, and this association did not vary by genetic predisposition to obesity among Korean adults.