ArticleNature2013
A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 12 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 12 syntheses or guidelines pooled it, 233 citations in OpenAlex.
- Advances in statin adverse reactions and the potential mechanisms: A systematic review.Journal of advanced research · 2025Pooled it
- Correlation between single-nucleotide polymorphisms and statin-induced myopathy: a mixed-effects model meta-analysis.European journal of clinical pharmacology · 2021Pooled it
- The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis.European journal of clinical pharmacology · 2021Pooled it
- Genetic variants modulate gene expression statin response in human lymphoblastoid cell lines.BMC genomics · 2020Pooled it
- Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.Clinical pharmacology and therapeutics · 2019Pooled it
- Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing.PloS one · 2019Pooled it
- A comprehensive review and meta-analysis of risk factors for statin-induced myopathy.European journal of clinical pharmacology · 2018 · on this mapPooled it
- Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence.Cardiovascular research · 2018Pooled it
- GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.Cell metabolism · 2015Pooled it
- Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2014Pooled it
- Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.American journal of human genetics · 2014Pooled it
- The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review.PharmacogenomicsPooled it
- Pharmacogenomic Study of Statin-Associated Muscle Symptoms in the ODYSSEY OUTCOMES Trial.Circulation. Genomic and precision medicine · 2022Trial
- ZNF542P is a pseudogene associated with LDL response to simvastatin treatment.Scientific reports · 2018Trial
- Study of Estrogen Receptor-Mediated PGx-eQTLs Identifies Genetic Determinants of Breast Cancer Endocrine Therapy Response.International journal of molecular sciences · 2026Article
- Polygenic risk scores in pharmacogenomics: methodological challenges, current applications, and perspectives for clinical implementation.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- GATM alleviates sepsis-induced acute kidney injury via PDK4-mediated glycolytic reprogramming in renal tubular epithelial cells.Cellular and molecular life sciences : CMLS · 2026Article
- Host genotypes interact with microbial communities to modulate gene expression in the human intestine.medRxiv : the preprint server for health sciences · 2026Article
- Statins in Acute Ischemic Stroke: Mechanisms, Resistance, and Precision Strategies for Neurovascular and Cognitive Protection.CNS drugs · 2025Review
- Mechanisms of Homoarginine: Looking Beyond Clinical Outcomes.Acta physiologica (Oxford, England) · 2025Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 12 institutions in 2 countries.
Funding
Abstract
Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk and have been shown to have beneficial effects in a broad range of patients. However, statins are associated with an increased risk, albeit small, of clinical myopathy and type 2 diabetes. Despite evidence for substantial genetic influence on LDL concentrations, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy or toxicity, and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment. This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.