Interactions between genetic predisposition to obesity, insulin resistance and type 2 diabetes risk, and food or beverage intake for incident type 2 diabetes: European Prospective Investigation into Cancer and Nutrition (EPIC) InterAct case-cohort study

Abstract

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.

Keywords: diabetes; diet; effect modification; epidemiology; gene–diet interaction; insulin resistance; nutritional epidemiology; obesity; polygenic risk score; precision nutrition.