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Habitual coffee consumption and its association with health outcomes may be modified by genetic variation. Adults aged 40 to 69 years who participated in the Korea Association Resource (KARE) study were included in this study. We conducted a genome-wide association study (GWAS) on coffee consumption in 7868 Korean adults, and examined whether the association between coffee consumption and the risk of prediabetes and type 2 diabetes combined was modified by the genetic variations in 4054 adults. In the GWAS for coffee consumption, a total of five single nucleotide polymorphisms (SNPs) located in 12q24.11-13 (rs2074356, rs11066015, rs12229654, rs11065828, and rs79105258) were selected and used to calculate weighted genetic risk scores. Individuals who had a larger number of minor alleles for these five SNPs had higher genetic risk scores. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) to examine the association. During the 12 years of follow-up, a total of 2468 (60.9%) and 480 (11.8%) participants were diagnosed as prediabetes or type 2 diabetes, respectively. Compared with non-black-coffee consumers, the OR (95% CI) for ≥2 cups/day by black-coffee consumers was 0.61 (0.38-0.95; p for trend = 0.023). Similarly, sugared coffee showed an inverse association. We found a potential interaction by the genetic variations related to black-coffee consumption, suggesting a stronger association among individuals with higher genetic risk scores compared to those with lower scores; the ORs (95% CIs) were 0.36 (0.15-0.88) for individuals with 5 to 10 points and 0.87 (0.46-1.66) for those with 0 points. Our study suggests that habitual coffee consumption was related to genetic polymorphisms and modified the risk of prediabetes and type 2 diabetes combined in a sample of the Korean population. The mechanisms between coffee-related genetic variation and the risk of prediabetes and type 2 diabetes combined warrant further investigation.

Interactions of Habitual Coffee Consumption by Genetic Polymorphisms with the Risk of Prediabetes and Type 2 Diabetes Combined