ArticleJournal of lipid research2012
Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a).
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 6 of them syntheses that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 6 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Genetic variants modulate gene expression statin response in human lymphoblastoid cell lines.BMC genomics · 2020Pooled it
- A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering.Pharmacogenomics · 2016Pooled it
- Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.Nature communications · 2014Pooled it
- Robust association of the LPA locus with low-density lipoprotein cholesterol lowering response to statin treatment in a meta-analysis of 30 467 individuals from both randomized control trials and observational studies and association with coronary artery disease outcome during statin treatment.Pharmacogenetics and genomics · 2013 · on this mapPooled it
- Positive correlation between variants of lipid metabolism‑related genes and coronary heart disease.Molecular medicine reports · 2013Pooled it
- The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review.PharmacogenomicsPooled it
- ZNF542P is a pseudogene associated with LDL response to simvastatin treatment.Scientific reports · 2018Trial
- Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging.Atherosclerosis · 2016 · on this mapTrial
- Ancestry and other genetic associations with plasma PCSK9 response to simvastatin.Pharmacogenetics and genomics · 2014Trial
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- Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.European heart journal · 2013Trial
- Polygenic Prediction of Nongoal Response to Statin Therapy.Circulation. Genomic and precision medicine · 2026Article
- Pharmacogenomic predictors of drug response and choice in dyslipidemia and hypertension.medRxiv : the preprint server for health sciences · 2026Article
- Improving polygenic risk score based drug response prediction using transfer learning.NPJ genomic medicine · 2025Article
- Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.Nature communications · 2025Article
- Characterizing the genetic architecture of drug response using gene-context interaction methods.Cell genomics · 2024Article
- Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response.Genome medicine · 2024Article
- Novel Therapeutic Approaches for the Management of Elevated Lipoprotein(a): From Traditional Agents to Future Treatment Options.Life (Basel, Switzerland) · 2024Review
- Association ofPeerJ · 2024Article
Corrections and comments
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Authors and funding
24 authors at 12 institutions in 4 countries.
Funding
Abstract
We carried out a genome-wide association study (GWAS) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study (CARDS; n = 1,156), the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n = 895), and the observational phase of ASCOT (n = 651), all of whom were prescribed atorvastatin 10 mg. Following genome-wide imputation, we combined data from the three studies in a meta-analysis. We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 (P = 6.13 × 10(-9)) within the LPA gene and at two single nucleotide polymorphisms (SNP) within the APOE region (rs445925; P = 2.22 × 10(-16) and rs4420638; P = 1.01 × 10(-11)) that are proxies for the ε2 and ε4 variants, respectively, in APOE. The novel association with the LPA SNP was replicated in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (P = 0.009). Using CARDS data, we further showed that atorvastatin therapy did not alter lipoprotein(a) [Lp(a)] and that Lp(a) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels. However, statin therapy had a similar effect in reducing cardiovascular disease (CVD) in patients in the top quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower three quartiles (HR = 0.66; P = 0.8 for interaction). The data emphasize that high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response. Therefore, an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a). However, statin therapy seems beneficial even in those with high Lp(a).
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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.