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. 2025 Aug 20;64(6):263.
doi: 10.1007/s00394-025-03782-y.

Interaction between coffee consumption and polygenic risk score in relation to diabetes: insights from the Maastricht study

Yufeng Rao  1   2 , Evan Yi-Wen Yu  1   3 , Tzu-Yao Lin  4   5   6 , Yiming Chen  1   2 , Yingfen Qin  7 , Annemarie Koster  5   8 , Simone J P M Eussen  1   5   9 , Hans Bosma  5   8 , Tos T J M Berendschot  2   10   11 , Carla J H van der Kallen  9   12 , Marleen M J van Greevenbroek  9   12 , Bastiaan E de Galan  9   12   13 , Maurice P Zeegers  1   2   5 , Anke Wesselius  14   15
Affiliations

Interaction between coffee consumption and polygenic risk score in relation to diabetes: insights from the Maastricht study

Yufeng Rao et al. Eur J Nutr. .

Abstract

Aims: This study investigated the associations of polygenic risk score (PRS) and coffee consumption, as well as their interaction, with prediabetes and type 2 Diabetes Mellitus (T2DM) among participants in the southern Netherlands.

Methods: 7668 participants were classified as normal glucose metabolism (NGM), prediabetes, or T2DM based on World Health Organization 2006 criteria. PRS (423 T2DM-related single nucleotide polymorphisms) and coffee consumption (via food frequency questionnaire) were categorized into tertiles (low, medium, and high) based on the population distribution. Multinomial logistic regression and dose-response analyses were performed to evaluate the cross-sectional associations between PRS and coffee consumption with prediabetes and T2DM.

Results: Fully adjusted analyses indicated that medium and high coffee consumption were associated with lower odds of prediabetes (odds ratios [ORs]: 0.80; 95% CI: 0.69, 0.92 and 0.83; 95% CI: 0.72, 0.96) and T2DM (ORs: 0.80; 95% CI: 0.70, 0.91 and 0.80; 95% CI: 0.70, 0.91). U-shaped associations were observed for both prediabetes and T2DM, with the overlapping range of 2.9-6.9 cups/day statistically associated with lower odds (OR < 1) for both conditions. Additionally, participants in the PRS group had higher odds of prediabetes (OR: 1.58; 95% CI: 1.35, 1.86) and T2DM (OR: 3.16; 95% CI: 2.80, 3.56) compared to the low PRS group. No significant interaction was found between PRS and coffee consumption (P = 0.21).

Conclusions: No significant interaction was observed between coffee consumption and PRS for prediabetes and T2DM. Coffee consumption was associated with the prevalence of both conditions in a pattern that may be U-shaped. However, these associations appear to be population-specific and require validation in diverse populations to clarify gene-lifestyle interactions.

Keywords: Coffee consumption; Dose–response; Polygenic risk score; Prediabetes; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Dose–response association between coffee consumption and the prevalence of prediabetes (n = 6027) and T2DM (n = 6509). The dose–response associations between coffee consumption and the prevalence of prediabetes (panel a) and T2DM (panel b) were modeled using restricted cubic splines with 4 knots placed at the 5th, 35th, 65th, 95th percentiles of coffee consumption. The reference was set at the 5th percentile, corresponding to approximately 0 cups/day in both panels. Models were adjusted age, sex, educational level, body mass index (BMI), alcohol consumption, smoking status, number of steps while awake, Dutch Healthy Diet (DHD), energy intake, cardiovascular disease (CVD), serum total cholesterol, mean arterial pressure, use of blood pressure lowering medication, use of lipid-modification medication, sugar consumption, and family history of diabetes. The solid blue line indicates ORs, the blue shaded area indicates 95% Cis. OR, odds ratio; CI, confidence interval
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