The heritability levels of two traits for diabetes diagnosis, fasting serum glucose (FG) and glycated hemoglobin (HbA1c), were estimated to be 51% ∼ 62%. Studies have shown that cigarette smoking is a modifiable risk factor for diabetes. It is important to uncover whether smoking may modify the genetic risk of diabetes. This study included a discovery cohort (TWB1) of 25,460 and a replication cohort (TWB2) of 58,774 unrelated Taiwan Biobank subjects. Genetic risk score (GRS) of each TWB2 subject was calculated with weights retrieved from TWB1 analyses. We then assessed the significance of GRS-smoking interactions on FG/HbA1c/diabetes while adjusting for covariates. A total of 5 smoking measurements were investigated respectively, including "active smoking status", "pack-years", "years as a smoker", "packs smoked per day", and "hours as a passive smoker per week". Except passive smoking, all smoking measurements were associated with FG/HbA1c/diabetes (P < 0.0033) and were associated with an exacerbation of the genetic risk of FG/HbA1c (P (Interaction) < 0.0033). For example, each 1 standard deviation increase in GRS is associated with a 1.68% higher FG in subjects consuming one more pack of cigarettes per day (P (Interaction) = 1.9×10(-7)). Smoking cessation is especially important for people who are more genetically predisposed to diabetes.
