Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps

作者：Ference Brian A

来源：Current Opinion in Lipidology, 2015, 26(6): 566-571.

DOI：10.1097/MOL.0000000000000247

• coronary heart disease
• low-density lipoprotein cholesterol
• Mendelian randomization
• statins

Purpose of reviewMendelian randomization studies have the potential to transform our understanding of cardiovascular medicine by generating naturally randomized data that can fill evidence gaps when a randomized trial would be either impossible or impractical to conduct. Here, we review recent Mendelian randomization studies evaluating the effect of low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD).Recent findingsMendelian randomization studies consistently demonstrate that LDL-C is causally associated with the risk of CHD. Furthermore, exposure to genetically mediated lower LDL-C appears to be associated with a much greater than expected reduction in CHD risk, thus suggesting that LDL-C has a cumulative effect on the risk of CHD. In addition, genetically mediated lower LDL-C is log-linearly associated with the risk of CHD and the effect of polymorphisms in multiple different genes on the risk of CHD is remarkably consistent when measured per unit lower LDL-C.SummaryThe naturally randomized genetic evidence suggests that LDL-C has a causal and cumulative effect on the risk of CHD, and that the clinical benefit of exposure to lower LDL-C is determined by the absolute magnitude of exposure to lower LDL-C independent of the mechanism by which LDL-C is lowered.

• 出版日期2015-12