statin_pleiotropic_effects

Exploring Statin Pleiotropic Effects within a Very Large EHR Cohort

Statins among the most widely prescribed agents worldwide for prevention of cardiovascular diseases, produce substantial pleiotropic effects. Pleiotropic effects are unanticipated outcomes other than those for which the drug was originally developed, either therapeutic (beneficial) or detrimental (adverse drug reactions). Statin pleiotropic effects are unanticipatedly broad, including increasing the risk of developing type 2 diabetes mellitus and cataract, decreasing cancer-related mortality, and reducing dementia. Many effects are still not determined. We investigate statin pleiotropic effects using whole de-identified electronic health records (EHRs) of >2 million patients at Vanderbilt (including 10,000 genotyped statin recipients) to answer these questions.

 

Relevant citations:

  • Wei WQ, Li X, Feng Q, Kubo M, Kullo IJ, Peissig PL, Karlson EW, Jarvik GP, Lee MTM, Shang N, Larson EA, Edwards T, Shaffer C, Mosley JD, Maeda S, Horikoshi M, Ritchie M, Williams MS, Larson EB, Crosslin DR, Bland ST, Pacheco JA, Rasmussen-Torvik LJ, Cronkite D, Hripcsak G, Cox NJ, Wilke RA, Stein CM, Rotter JI, Momozawa Y, Roden DM, Krauss RM, Denny JC.. LPA Variants are Associated with Residual Cardiovascular Risk in Patients Receiving Statins. Circulation. 2018;CIRCULATIONAHA.117.031356
  • Zhao J, Feng Q, Wu P, Warner JL, Denny JC, Wei WQ. Using topic modeling via non-negative matrix factorization to identify relationships between genetic variants and disease phenotypes: A case study of Lipoprotein(a) (LPA). PLoS One. 2019 Feb 13;14(2):e0212112. doi: 10.1371/journal.pone.0212112. eCollection 2019. PMID: 30759150 PMCID: PMC6374022
  • Feng Q, Wei WQ, Chung CP, Levinson RT, Sundermann AC, Mosley JD, Bastarache L, Ferguson JF, Cox NJ, Roden DM, Denny JC, Linton MF, Edwards DRV, Stein CM. Relationship between very low low-density lipoprotein cholesterol concentrations not due to statin therapy and risk of type 2 diabetes: A US-based cross-sectional observational study using electronic health records. PLoS Med. 2018 Aug 28;15(8):e1002642. doi: 10.1371/journal.pmed.1002642. eCollection 2018 Aug. PMID: 30153257
  • Qiping Feng, Wei-Qi Wei, Cecilia Chung, Rebecca Levinson, Lisa Bastarache, Joshua Denny, and Michael Stein. The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy. The Pharmacogenomics Journal, 2017 Mar;17(2):204-208.