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Initiation of smoking and susceptibility to type 2 diabetes: a mendelian randomization study

By Christopher S Thom, Zhuoran Ding, Michael G. Levin, Scott M. Damrauer, Benjamin F. Voight

Posted 03 Feb 2020
medRxiv DOI: 10.1101/2020.01.30.20019737

ObjectivesTo evaluate the association between smoking behavior and type 2 diabetes risk using genetic data. Research Design and MethodsWe obtained summary data from genome-wide association studies (GWAS) related to smoking behavior (n=1.2 million people) and type 2 diabetes (n=898,130) in individuals of European ancestry. Mendelian randomization analysis was performed using these summary-level statistics. Specifically, we assessed if genetically determined smoking initiation, smoking cessation, and smoking heaviness (number of cigarettes per day) modulated susceptibility to type 2 diabetes. ResultsWe observed that for each 2-fold increased odds of initiating smoking behavior corresponded with a 21% increased susceptibility to type 2 diabetes (OR = 1.21, 95% CI: 1.18-1.24, P=1x10-12). Our effect was consistent across instrumental variable methodological approaches, and we did not observe evidence of systematic biases to our effect estimate. When analyzed using an analogous approach, we found that the effect of smoking initiation increasing diabetes risk was equivalent to the effect of smoking behavior on increase coronary artery disease, an established causal risk factor for cardiovascular disease. ConclusionsGenetic data supports the hypothesis that smoking initiation corresponds with increased risk for type 2 diabetes. These findings are consistent with previous clinical epidemiological association between smoking behavior and elevated type 2 diabetes risk. Individual-level MR studies are necessary to estimate mediators and confounders related to this association.

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