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  • Statin-induced LDL choleste...
    Smit, Roelof A J; Trompet, Stella; Leong, Aaron; Goodarzi, Mark O; Postmus, Iris; Warren, Helen; Theusch, Elizabeth; Barnes, Michael R; Arsenault, Benoit J; Li, Xiaohui; Feng, QiPing; Chasman, Daniel I; Cupples, L Adrienne; Hitman, Graham A; Krauss, Ronald M; Psaty, Bruce M; Rotter, Jerome I; Cessie, Saskia le; Stein, C Michael; Jukema, J Wouter

    Pharmacogenomics journal, 06/2020, Letnik: 20, Številka: 3
    Journal Article

    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, n  = 40,914) and DIAGRAM (n  = 159,208) consortia, we found a positive genetic correlation between LDL-C statin response and T2D using LD score regression (r  = 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.