Journal
DIABETES
Volume 69, Issue 12, Pages 2819-2829Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db20-0156
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- Ministry of Science and Technology, Taiwan [MOST 107-2314-B-002-195-MY3]
- MOST [MOST 107-2314-B-002-195-MY3, MOST 102-2314-B-002-117-MY3]
- National Taiwan University Hospital [UN106-050]
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The heritability levels of two traits for diabetes diagnosis, serum fasting glucose (FG) and glycated hemoglobin (HbA(1c)), 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 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, HbA(1c), 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, HbA(1c), and diabetes (P < 0.0033) and were associated with an exacerbation of the genetic risk of FG and HbA(1c) (P-Interaction < 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 (P-Interaction = 1.9 x 10(-7)). Smoking cessation is especially important for people who are more genetically predisposed to diabetes.
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