Causal relationship between smoking behaviors on Graves disease: A two-sample mendelian randomization

Background/AimThe potential link between smoking and the susceptibility to Graves disease (GD) has been scrutinized in observational studies, yielding inconsistent results. We conducted a Mendelian randomization (MR) analysis to ascertain the causal relationship between smoking behaviors and the risk of GD. MethodThe data on smoking behaviors, including smoking initiation and lifetime smoking, were obtained from the published GWAS of individuals of European descent who participated in the GSCAN consortium. The genetic variants associated with Graves disease were identified using a GWAS of 458,620 participants of European descent from the UK Biobank. ResultsOur results show that smoking initiation was associated with GD [OR= 1.50, 95% CI (1.03,2.18), SE{square}={square}0.199, Pbeta{square}={square}0.031; Cochrans Q=36.62, p=0.999, I2=0.0%; MR-Eggerintercept= 0.003, p= 0.879], and lifetime smoking [OR{square}={square}3.42, 95% CI (1.56, 7.50), SE{square}={square}0.39, Pbeta<0.01; Cochrans Q=62.68, p=0.99, I2=0.0%; Eggerintercept=0.012, p=0.49]. All other MR methods, as well as sensitivity analysis results, were consistent in terms of betas and significance levels. ConclusionOur findings lend support to a causal relationship between smoking behaviors and the risk of Graves disease. These observations raise important questions about the role of smoking in the progression of GD. So, further investigation is clinically necessary to clarify the links between smoking and GD, which could inform health policy decisions aimed at reducing the risk of GD.