Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study

Research output: Contribution to journalArticle

Authors

  • on behalf of the GIST consortium

External Institution(s)

  • Leiden University
  • Harvard University
  • Cedars-Sinai Medical Center
  • Queen Mary University of London
  • Université Laval
  • University of California at Los Angeles
  • Vanderbilt University
  • Boston University
  • National Institutes of Health
  • Children's Hospital Oakland Research Institute
  • University of Washington
  • Kaiser Permanente

Details

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalPharmacogenomics Journal
Volume20
Issue number3
StatusPublished - Jun 1 2020
Peer-reviewedYes

Abstract

It remains unclear whether the increased risk of new-onset type 2 diabetes (T2D) seen in statin users is due to low LDL-C concentrations, or due to the statin-induced proportional change in LDL-C. In addition, genetic instruments have not been proposed before to examine whether liability to T2D might cause greater proportional statin-induced LDL-C lowering. Using summary-level statistics from the Genomic Investigation of Statin Therapy (GIST, nmax = 40,914) and DIAGRAM (nmax = 159,208) consortia, we found a positive genetic correlation between LDL-C statin response and T2D using LD score regression (rgenetic = 0.36, s.e. = 0.13). However, mendelian randomization analyses did not provide support for statin response having a causal effect on T2D risk (OR 1.00 (95% CI: 0.97, 1.03) per 10% increase in statin response), nor that liability to T2D has a causal effect on statin-induced LDL-C response (0.20% increase in response (95% CI: −0.40, 0.80) per doubling of odds of liability to T2D). Although we found no evidence to suggest that proportional statin response influences T2D risk, a definitive assessment should be made in populations comprised exclusively of statin users, as the presence of nonstatin users in the DIAGRAM dataset may have substantially diluted our effect estimate.

Citation formats

APA

Harvard