Genome-wide association study of statin-induced myopathy in patients recruited using the UK clinical practice research datalink

Statins can be associated with myopathy. We have undertaken a Genome-wide Association Study (GWAS) to discover and validate genetic risk-factors for statin-induced myopathy in a "real-world" setting. 135 statin myopathy patients recruited via the UK Clinical Practice Research Datalink were genotyped using the Illumina OmniExpress Exome v1.0 Bead Chip, and compared to the Wellcome Trust Case-Control Consortium (n=2501). Nominally statistically significant SNP signals in the GWAS (p<5x10-5 ) 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 genome-wide significant in the severe myopathy (CK>10xULN or rhabdomyolysis) group (p=2.55x10-9 ; OR 5.15, 95%CI 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. This article is protected by copyright. All rights reserved.