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

TL;DR

This study found no evidence that genetic predisposition to obesity or diabetes changes how diet affects type 2 diabetes risk in Europeans.

Contribution

The study is the first to systematically evaluate gene-diet interactions for type 2 diabetes using polygenic risk scores in a large European cohort.

Findings

No statistical interactions were found between genetic risk scores and dietary factors for type 2 diabetes.

Current polygenic risk score methods may lack the power to detect gene-diet interactions.

Dietary guidelines for diabetes prevention may not need to be tailored based on genetic predisposition.

Abstract

Limited evidence exists for effect modification of genetic characteristics on the associations of food consumption and incident type 2 diabetes (T2D).

We aimed to investigate whether the food-T2D association would vary by genetic susceptibility to metabolic traits.

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.

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).

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.

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