Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study.
dc.contributor.author | Smit, RAJ | en_US |
dc.contributor.author | Trompet, S | en_US |
dc.contributor.author | Leong, A | en_US |
dc.contributor.author | Goodarzi, MO | en_US |
dc.contributor.author | Postmus, I | en_US |
dc.contributor.author | Warren, H | en_US |
dc.contributor.author | Theusch, E | en_US |
dc.contributor.author | Barnes, MR | en_US |
dc.contributor.author | Arsenault, BJ | en_US |
dc.contributor.author | Li, X | en_US |
dc.contributor.author | Feng, Q | en_US |
dc.contributor.author | Chasman, DI | en_US |
dc.contributor.author | Cupples, LA | en_US |
dc.contributor.author | Hitman, GA | en_US |
dc.contributor.author | Krauss, RM | en_US |
dc.contributor.author | Psaty, BM | en_US |
dc.contributor.author | Rotter, JI | en_US |
dc.contributor.author | Cessie, SL | en_US |
dc.contributor.author | Stein, CM | en_US |
dc.contributor.author | Jukema, JW | en_US |
dc.contributor.author | GIST consortium | en_US |
dc.date.accessioned | 2020-01-03T17:51:07Z | |
dc.date.available | 2019-11-17 | en_US |
dc.date.issued | 2019-12-05 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/62179 | |
dc.description.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. | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Pharmacogenomics J | en_US |
dc.title | Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/s41397-019-0125-x | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31801993 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2019-11-17 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |