Cited 13 times since 2019 (3 per year) source: EuropePMC The pharmacogenomics journal, Volume 20, Issue 3, 5 1 2019, Pages 462-470 Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study. Smit RAJ, Trompet S, Leong A, Goodarzi MO, Postmus I, Warren H, Theusch E, Barnes MR, Arsenault BJ, Li X, Feng Q, Chasman DI, Cupples LA, Hitman GA, Krauss RM, Psaty BM, Rotter JI, Cessie SL, Stein CM, Jukema JW, GIST consortium
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.
