Trial reportBMC medical genetics2011
Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses.
Trial report in BMC medical genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis 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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Genome-wide association studies identify genetic loci for low von Willebrand factor levels.European journal of human genetics : EJHG · 2016Pooled it
- Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease.American journal of respiratory and critical care medicine · 2012Trial
- Genetic variant panel allows predicting both obesity risk, and efficacy of procedures and diet in weight loss.Frontiers in nutrition · 2023Article
- Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes in 454,193 Individuals Across 13 Cohorts.Diabetes care · 2022Article
- Common Genetic Variation in MC4R Does Not Affect Atherosclerotic Plaque Phenotypes and Cardiovascular Disease Outcomes.Journal of clinical medicine · 2021Article
- Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond.International journal of molecular sciences · 2019Review
- Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.Lipids in health and disease · 2018Article
- Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.Lipids in health and disease · 2017Article
- Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies.European journal of clinical pharmacology · 2016Article
- Association of common variants in TOMM40/APOE/APOC1 region with human longevity in a Chinese population.Journal of human genetics · 2016Article
- Potential Signals of Natural Selection in the Top Risk Loci for Coronary Artery Disease: 9p21 and 10q11.PloS one · 2015Article
- Article
- Genetic association analysis and meta-analysis of imputed SNPs in longitudinal studies.Genetic epidemiology · 2013Article
- Pharmacogenetics and cardiovascular disease--implications for personalized medicine.Pharmacological reviews · 2013Review
- Review of the cost effectiveness of pharmacogenetic-guided treatment of hypercholesterolaemia.PharmacoEconomics · 2013Review
- PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.Journal of lipid research · 2013Article
- Article
- Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a).Journal of lipid research · 2012Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundThe PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.
methodsThe genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.
resultsForty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.
conclusionWith the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.
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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.