Diet, Genes, or Both? Coffee Consumption, Snacking, and BDNF and TCF7L2 Genotypes in Relation to Cardiometabolic Traits: A Cross-Sectional Study in Polish Adults

Background/Objectives: Coffee consumption and snacking are common dietary behaviours linked to cardiometabolic risk, and variants in BDNF and TCF7L2 have been associated with obesity and type 2 diabetes (T2DM). We examined whether glycaemic, adiposity, and lipid traits reflect these behaviours, these genotypes, or both, and whether BDNF (rs10501087) and TCF7L2 (rs4506565, rs7901695, rs7903146) genotypes modify the behavioural associations. Methods: In a cross-sectional study of Polish adults (NCT03792685; analytic cohort n = 1227), coffee consumption (never, weekly, daily) and snacking frequency (rare, frequent) were assessed by questionnaire (n = 905); outcomes were glucose and insulin area under the curve (AUC) from a 2-h 75 g oral glucose tolerance test (OGTT), glycated haemoglobin (HbA1c), fasting lipids, and bioimpedance body composition. Multivariable models were adjusted for age, sex, daily energy intake, and physical inactivity; all analyses, including gene × behaviour interaction tests, were exploratory, with false discovery rate (FDR) correction for multiple testing. Results: Daily coffee consumption was associated with a higher glucose AUC than never consumption (β = +0.045, 95% confidence interval [CI] 0.018–0.073; p = 0.001; FDR q = 0.094), with higher post-load glucose and insulin but similar fasting glucose and HbA1c; the association was robust in sensitivity analyses. Weekly coffee consumption was associated with higher high-density lipoprotein cholesterol (β = +4.75 mg/dL, 95% CI 1.49–8.02; p = 0.004; FDR q = 0.10). Frequent snacking was associated with higher body mass index, fat mass, and body fat percentage (nominal p = 0.034–0.049; FDR q = 0.26) and was not associated with coffee consumption. BDNF rs10501087 CT was nominally associated with lower T2DM odds than TT (odds ratio [OR] = 0.42, 95% CI 0.21–0.78; p = 0.009). The behavioural associations showed no detectable modification by genotype (184 interaction tests; none with FDR q < 0.05). Conclusions: Everyday dietary behaviour, particularly daily coffee consumption, was more consistently related to cardiometabolic traits than BDNF or TCF7L2 genotypes. The post-load glycaemic profile of daily coffee consumers, missed by fasting glucose and HbA1c, highlights the value of OGTT-based phenotyping in nutritional research. These exploratory findings do not support genotype-tailored advice on coffee or snacking.