BACKGROUND: Limited evidence exists for effect modification of genetic characteristics on the associations of food consumption and incident type 2 diabetes (T2D). OBJECTIVES: We aimed to investigate whether the food-T2D association would vary by genetic susceptibility to metabolic traits. METHODS: We analyzed data from 9542 incident T2D cases and a subcohort of 12,477 participants nested within the 340,234-participant cohort recruited in 1991-1998 and followed up for 10.9 y on average in 8 European countries. Polygenic risk scores (PRSs) for higher body mass index, insulin resistance, and T2D were constructed. Fifteen dietary variables potentially associated with T2D, obtained with cohort-specific self-reported dietary assessment, were examined: fruits, green leafy vegetables, root vegetables, wholegrains, rice, legumes, nuts and seeds, fermented dairy, red meat, processed meat, fish, eggs and egg products, sugar-sweetened beverages, coffee, and tea. A cross-product term between each PRS and each food/beverage was evaluated by genotyping chip and country with Prentice-weighted Cox regression for incident T2D, and stratum-specific estimates were meta analyzed, followed by Benjamini-Yekutieli multiple-testing correction. RESULTS: Accounting for multiple tests of 3 PRSs × 15 dietary items, no evidence of statistical interaction was evident on either a multiplicative or additive scale, with exp(β for a multiplicative interaction) (95% confidence interval) ranging from 0.84 (0.64, 1.10) (root vegetables and PRS for T2D) to 1.45 (0.78-2.76) (fish and PRS for T2D). CONCLUSIONS: Genetic susceptibility to high-risk metabolic traits did not modify the diet-T2D associations in European populations. Acknowledging the limitations of current PRS-based methods to detect gene-diet interactions, research should continue into the potential for precision nutrition and tailored food-based dietary guidance for T2D prevention.
Journal article
2026-03-01T00:00:00+00:00
123
diabetes, diet, effect modification, epidemiology, gene–diet interaction, insulin resistance, nutritional epidemiology, obesity, polygenic risk score, precision nutrition, Humans, Diabetes Mellitus, Type 2, Female, Male, Middle Aged, Insulin Resistance, Genetic Predisposition to Disease, Prospective Studies, Diet, Europe, Obesity, Adult, Risk Factors, Beverages, Incidence, Aged, Cohort Studies, Body Mass Index