A Mendelian Randomization Approach Using 3-HMG-Coenzyme-A Reductase Gene Variation to Evaluate the Association of Statin-Induced Low-Density Lipoprotein Cholesterol Lowering With Noncardiovascular Disease Phenotypes

Key Points Question Are there associations between candidate noncardiovascular diseases and statin treatment using genetic variants in the 3-hydroxy-3-methylglutaryl coenzyme A reductase ( HMGCR ) gene that decrease low-density lipoprotein cholesterol levels as an instrumental variable? Findings In a mendelian randomization approach cohort study including 53 385 individuals, using variants in the HMGCR gene affecting low-density lipoprotein cholesterol levels replicated the association between statin use and increased type 2 diabetes risk. However, no strong associations between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition by statins and other diseases were noted. Meaning In this cohort study, statin treatment was associated with an increased risk of type 2 diabetes, but there appeared to be no strong indication of other pleiotropic outcomes of the low-density lipoprotein cholesterol level–decreasing outcomes with this drug class on the clinical phenotypes studied.