Relationship between tobacco smoking and metabolic syndrome: a Mendelian randomization analysis

Numerous epidemiologic observational studies have demonstrated that smokers have an increased risk of developing cardiovascular-related diseases. However, less is known about the causal relationship between tobacco smoking and the metabolic syndrome. This study aimed to determine whether genetically predicted smoking is associated with metabolic syndrome using the Mendelian randomization (MR) approach.

This paper used individual-level genetic and personal data from the Taiwan Biobank dataset, including 80,072 Han Chinese individuals (15,773 cases of metabolic and 64,299 controls; 21,399 smokers and 58,673 nonsmokers). The literature was searched for smoking-associated single nucleotide polymorphisms (SNPs), and 14 SNPs satisfying MR assumptions were identified and used as instrumental variables. Weighted and unweighted genetic risk scores (GRSs) based on these significant SNPs were derived. MR analyses were performed using the two-stage approach of regression models.

Genetically predicted smoking is associated with a higher risk of metabolic syndrome (odds ratio [OR]: 1.49, 95% CI: 1.47-1.52 per 1 standard deviation increase) for weighted and unweighted GRSs. When Q1 was used as the reference group, the adjusted ORs of metabolic syndrome for Q2, Q3, and Q4 were 1.15 (1.08, 1.22), 2.17 (2.05, 2.30), and 4.23 (3.98, 4.49), respectively, for the weighted GRS. The corresponding ORs for Q2, Q3, and Q4 were 1.16 (1.09, 1.24), 2.17 (2.05, 2.30), and 4.26 (4.02, 4.53), respectively, for the unweighted GRS.

Genetic predisposition toward tobacco smoking is strongly associated with a higher likelihood of metabolic syndrome. Further work is warranted to clarify the underlying mechanism of smoking in the development of metabolic syndrome.