Active Cigarette Smoking Is Associated With an Exacerbation of Genetic Susceptibility to Diabetes

Abstract

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 5 1.9 3 10 -7 ). Smoking cessation is especially important for people who are more genetically predisposed to diabetes.

Associations of five obesity metrics with epigenetic age acceleration: Evidence from 2,474 Taiwan Biobank participants

“…DNAm occurs predominantly at cytosine‐phosphate‐guanine (CpG) sites (6). Environmental factors such as smoking are associated with changes in methylation levels (7‐10). In contrast with DNA sequences, which remain stable throughout the lifetime, DNAm levels are dynamic and they can reflect physiological alterations (11).…”

Interactive Effect of IGF2BP2 rs4402960 Variant, Smoking and Type 2 Diabetes

“…A recent replication study in Taiwan showed that genetic susceptibility to diabetes might be intensified by active smoking. 21 Most recently, genome-environment-wide interactive studies on T2D also provided evidence for genetic interactions with active smoking. 11 Despite these observations, the probable biologic pathways or regulatory mechanisms to clarify these associations remain to be determined.…”

“…The TWB research team obtained ethical approval for the program from the Ethics and Governance Council of Taiwan Biobank and the Institutional Review Board on Biomedical Science Research/IRB-BM in Academia Sinica. 21 Data from 52 participants were incomplete and hence were excluded. In the final analysis, data were from 22,039 participants (11,049 women and 10,990 men).…”

Interactive Association Between Intronic Polymorphism (rs10506151) of the LRRK2 Gene and Type 2 Diabetes on Neurodegenerative Diseases

“…The Institutional Review Board on Biomedical Science Research in Academia Sinica and the Governance Council of Taiwan Biobank had approved the TWB project. 19 Biobank participants had provided written informed consent before enrollment. This study was approved by the Institutional Review Board of Chung Shan Medical University (CS1-20009).…”

“…Details of the genotyping procedures have been described elsewhere. 19 In this study, we chose the LRRK2 rs10506151 variant based on its previous associations with neurodegenerative diseases. This variant passed the quality control test: call rate (>95%), Hardy-Weinberg equilibrium test (p>1.0 × 10 −3 ), and minor allele frequency (>0.05).…”