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Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study.
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| Title | Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Smit, RAJ, Trompet, S, Leong, A, Goodarzi, MO, Postmus, I, Warren, H, Theusch, E, Barnes, MR, Arsenault, BJ, Li, X, Feng, QP, Chasman, DI, Cupples, AL, Hitman, GA, Krauss, RM, Psaty, BM, Rotter, JI, le Cessie, S, C Stein, M, J Jukema, W |
| Corporate/Institutional Authors | GIST consortium |
| Journal | Pharmacogenomics J |
| Date Published | 2019 Dec 05 |
| ISSN | 1473-1150 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41397-019-0125-x |
| Alternate Journal | Pharmacogenomics J. |
| PubMed ID | 31801993 |
ePub date:
19/12