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OBJECTIVE To assess the interactions between diet quality and genetic predisposition to incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Between 2006 and 2010, 357,419 participants with genetic and complete dietary data from the UK Biobank were enrolled and prospectively followed up to 2017. The genetic risk score (GRS) was calculated on the basis of 424 variants associated with T2D risk, and a higher GRS indicates a higher genetic predisposition to T2D. The adherence to a healthy diet was assessed by a diet quality score comprising 10 important dietary components, with a higher score representing a higher overall diet quality. RESULTS There were 5,663 incident T2D cases documented during an average of 8.1 years of follow-up. A significant negative interaction was observed between the GRS and the diet quality score. After adjusting for major risk factors, per SD increment in the GRS and the diet quality score was associated with a 54% higher and a 9% lower risk of T2D, respectively. A simultaneous increment of 1 SD in both the diet quality score and GRS was additionally associated with a 3% lower T2D risk due to the antagonistic interaction. In categorical analyses, a sharp reduction of 23% in T2D risk associated with a 1-SD increment in the diet quality score was detected among participants in the extremely high GRS group (GRS &amp;gt;95%). We also observed a strong negative interaction between the GRS and the diet quality score on the blood HbA1c level at baseline (P &amp;lt; 0.001). CONCLUSIONS The adherence to a healthy diet was associated with more reductions in blood HbA1c levels and subsequent T2D risk among individuals with a higher genetic risk. Our findings support tailoring dietary recommendations to an individual’s genetic makeup for T2D prevention.

Effect of Diet Quality and Genetic Predisposition on Hemoglobin A1c and Type 2 Diabetes Risk: Gene-Diet Interaction Analysis of 357,419 Individuals