WAN-YU LINLiu Y.-L.Yang A.C.Tsai S.-J.PO-HSIU KUO2021-05-202021-05-2020200012-1797https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096515213&doi=10.2337%2fdb20-0156&partnerID=40&md5=ae84ddc0b89ceceaab3e567e1cfe4103https://scholars.lib.ntu.edu.tw/handle/123456789/561495The heritability levels of two traits for diabetes diagnosis, serum fasting 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 in-cluded unrelated Taiwan Biobank subjects in a discovery cohort (TWB1) of 25,460 subjects and a replication cohort (TWB2) of 58,774 subjects. Genetic risk score (GRS) of each TWB2 subject was calculated with weights retrieved from the TWB1 analyses. We then assessed the significance of GRS-smoking interactions on FG, HbA1c, and diabetes while adjusting for covariates. A total of five smoking measurements were investigated, including active smoking status, pack-years, years as a smoker, packs smoked per day, and hours as a passive smoker per week. Except for passive smoking, all smoking measurements were associated with FG, HbA1c, and diabetes (P < 0.0033) and were associated with an exacerbation of the genetic risk of FG and HbA1c (PInteraction < 0.0033). For example, each 1 SD increase in GRS is associated with a 1.68% higher FG in subjects consuming one more pack of cigarettes per day (PInteraction = 1.9 ? 10–7). Smoking cessation is especially important for people who are more genetically predisposed to diabetes. ? 2020 by the American Diabetes Association.[SDGs]SDG3glucose; hemoglobin A1c; adult; Article; biobank; cigarette smoking; cohort analysis; controlled study; diabetes mellitus; disease predisposition; DNA methylation; drinking behavior; education; exercise; fasting; female; genetic risk; genetic risk score; genetic susceptibility; glucose blood level; heritability; human; major clinical study; male; middle aged; passive smoking; people by smoking status; priority journal; risk factor; Taiwan; adverse event; aged; cigarette smoking; diabetes mellitus; genetic predisposition; genetics; single nucleotide polymorphism; Adult; Aged; Blood Glucose; Cigarette Smoking; Diabetes Mellitus; DNA Methylation; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotidejournal article10.2337/db20-0156330044712-s2.0-85096515213