Dataset Information

Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease.

ABSTRACT: Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants of smoking initiation increased risk for type 2 diabetes (OR 1.21, 95% CI: 1.15-1.27, P =?1?×?10-12) and coronary artery disease (CAD; OR 1.21, 95% CI: 1.16-1.26, P =?2?×?10-20). Additionally, 2-fold increased smoking risk was positively associated with increased BMI (~0.8 kg/m2, 95% CI: 0.54-0.98 kg/m2, P =?1.8?×?10-11). Multivariable Mendelian randomization analyses showed that BMI accounted for nearly all the risk smoking exerted on type 2 diabetes (OR 1.06, 95% CI: 1.01-1.11, P =?0.03). In contrast, the independent effect of smoking on increased CAD risk persisted (OR 1.12, 95% CI: 1.08-1.17, P =?3?×?10-8). Causal mediation analyses agreed with these estimates. Furthermore, analysis using individual-level data from the Million Veteran Program independently replicated the association of smoking behavior with CAD (OR 1.24, 95% CI: 1.12-1.37, P =?2?×?10-5), but not type 2 diabetes (OR 0.98, 95% CI: 0.89-1.08, P =?0.69), after controlling for BMI. Our findings support a model whereby genetic determinants of smoking increase type 2 diabetes risk indirectly through their relationship with obesity. Smokers should be advised to stop smoking to limit type 2 diabetes and CAD risk. Therapeutic efforts should consider pathophysiology relating smoking and obesity.

SUBMITTER: Thom CS

PROVIDER: S-EPMC7689293 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease.

Thom Christopher S CS Ding Zhuoran Z Levin Michael G MG Damrauer Scott M SM Lee Kyung Min KM Lynch Julie J Chang Kyong-Mi KM Tsao Philip S PS Cho Kelly K Wilson Peter W F PWF Assimes Themistocles L TL Sun Yan V YV O'Donnell Christopher J CJ Vujkovic Marijana M Voight Benjamin F BF

Human molecular genetics 20201101 19

Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants ...[more]

PMID: 32833022

Similar Datasets

Project description:The inferior border of the femoral head (IBFH) is widely used as a landmark in femoral artery puncture during invasive coronary angiography (ICA). However, application of this technique can be challenging especially in obese patients. This study was performed to investigate the association between body mass index (BMI) and the risk of low puncture in femoral artery puncture.A total of 464 patients (64.8?±?11.1 years, 55.8% male) who underwent ICA via trans-femoral access were retrospectively reviewed. IBFH was used as a landmark for a skin nick and the femoral artery cannulation site was confirmed by femoral angiography. Cannulation at the bifurcation of the common femoral artery (CFA) or below were considered low puncture.Twenty-nine patients (5.8%) were identified as having an angiographically high CFA bifurcation and low femoral artery puncture occurred in 27 (93.1%) patients of them. Among patients with normal bifurcation (n?=?464), low puncture occurred in 74 (15.9%) patients. Underweight (BMI < 18.5?kg/m) or obese (BMI ? 30?kg/m) patients were more common in the low puncture group than in the proper puncture group (36.5% vs. 5.9%, P < .001). Multivariable analysis showed underweight or obesity (odd ratio, 9.10; 95% confidential interval, 4.77-17.35; P?<?.001) was an independent risk factor of low puncture even after controlling for clinical covariates. The average distance from IBFH to the CFA puncture site was shorter in patients with underweight (1.74?±?0.71?cm) or obesity (1.75?±?0.60?cm) than in those with normal BMI or overweight (2.07?±?0.83?cm) (P?=?.030). Trigonometric calculation showed that the average distance from IBFH to the CFA puncture site was 0.5 to 2.59?cm (mean?=?1.32?cm) shorter in underweight patients compared with those of normal weight or overweight patients.In patients with normal CFA bifurcation, underweight or obesity were associated with increased risk of low puncture. The puncture site should be chosen about 1 finger width more proximal to IBFH for ICA in such patients.

Dataset Information

Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease.

Publications

Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets