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Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.

TitleGenomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.
Publication TypeJournal Article
Year of Publication2019
AuthorsCarr, DF, Francis, B, Jorgensen, AL, Zhang, E, Chinoy, H, Heckbert, SR, Bis, JC, Brody, JA, Floyd, JS, Psaty, BM, Molokhia, M, Lapeyre-Mestre, M, Conforti, A, Alfirevic, A, van Staa, T, Pirmohamed, M
JournalClin Pharmacol Ther
Volume106
Issue6
Pagination1353-1361
Date Published2019 12
ISSN1532-6535
KeywordsAdverse Drug Reaction Reporting Systems, Case-Control Studies, Databases, Factual, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver-Specific Organic Anion Transporter 1, Muscular Diseases, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Severity of Illness Index, United Kingdom
Abstract<p>Statins can be associated with myopathy. We have undertaken a genomewide association study (GWAS) to discover and validate genetic risk factors for statin-induced myopathy in a "real-world" setting. One hundred thirty-five patients with statin myopathy recruited via the UK Clinical Practice Research Datalink were genotyped using the Illumina OmniExpress Exome version 1.0 Bead Chip and compared with the Wellcome Trust Case-Control Consortium (n = 2,501). Nominally statistically significant single nucleotide polymorphism (SNP) signals in the GWAS (P < 5 × 10 ) were further evaluated in several independent cohorts (comprising 332 cases and 449 drug-tolerant controls). Only one (rs4149056/c.521C>T in the SLCO1B1 gene) SNP was genomewide significant in the severe myopathy (creatine kinase > 10 × upper limit of normal or rhabdomyolysis) group (P = 2.55 × 10 ; odds ratio 5.15; 95% confidence interval 3.13-8.45). The association with SLCO1B1 was present for several statins and replicated in the independent validation cohorts. The data highlight the role of SLCO1B1 c.521C>T SNP as a replicable genetic risk factor for statin myopathy. No other novel genetic risk factors with a similar effect size were identified.</p>
DOI10.1002/cpt.1557
Alternate JournalClin Pharmacol Ther
PubMed ID31220337
PubMed Central IDPMC6896237
Grant ListMC_QA137929 / / Medical Research Council / United Kingdom
MR/L006758/1 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
/ / Department of Health / United Kingdom
ePub date: 
19/06