title: Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps.
abstract: OBJECTIVE
  Mendelian 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).
  
  
  RESULTS
  Mendelian 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Division of Translational Research and Clinical Epidemiology, Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Ference
mesh_terms: D000081:Acetamides; D008078:Cholesterol, LDL / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057182:Mendelian Randomization Analysis / Q000379:methods*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000081:Acetamides; D008078:Cholesterol, LDL; C009158:CDAA