Evidence map›Paper›PMID 39798939›Full record

SynthesisPharmacological research2025

GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.

Emma F Magavern, Harshal Deshmukh, Geraldine Asselin, Elizabeth Theusch, Stella Trompet, Xiaohui Li, Raymond Noordam, Y-D Ida Chen, Teresa E Seeman, Kent D Taylor and 17 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Pharmacological research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Emma F MagavernCentre of Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, UK.
Harshal DeshmukhMackay Base Hospital, Queensland Health, Queensland, Australia.
Geraldine AsselinFaculty of Medicine, Université de Montréal, and the Montreal Heart Institute, Montreal, Canada.
Elizabeth TheuschDepartment of Pediatrics, University of California San Francisco, Oakland, CA, United States.
Stella TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Xiaohui LiInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Y-D Ida ChenInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Teresa E SeemanDivision of Geriatrics, Dept of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Wendy S PostDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Jean-Claude TardifFaculty of Medicine, Université de Montréal, and the Montreal Heart Institute, Montreal, Canada.
Dirk S PaulCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Cambridge, UK.
Emelia J BenjaminBoston University Chobanian & Avedisian School of Medicine and School of Public Health, NHLBI and Boston University's Framingham Heart Study, Framingham, MA, United States.
Nancy L Heard-CostaBoston University Chobanian & Avedisian School of Medicine and School of Public Health, NHLBI and Boston University's Framingham Heart Study, Framingham, MA, United States.
Ramachandran S VasanBoston University Chobanian & Avedisian School of Medicine and School of Public Health, NHLBI and Boston University's Framingham Heart Study, Framingham, MA, United States.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Ronald M KraussDepartment of Pediatrics, University of California San Francisco, Oakland, CA, United States.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Patricia B MunroeCentre of Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, UK.
Mark J CaulfieldCentre of Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, UK.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Marie-Pierre DubéFaculty of Medicine, Université de Montréal, and the Montreal Heart Institute, Montreal, Canada.
Graham A HitmanCentre of Genomic Medicine and Child Health, Blizard Institute, Queen Mary University of London, London, UK.
Helen R WarrenCentre of Clinical Pharmacology & Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, UK; NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, UK. Electronic address: h.r.warren@qmul.ac.uk.
Genomic Investigation of Statin Therapy Consortium (GIST)

Funding

NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U19 HL069757
6 · The paper itself

Abstract

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P < 5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P < 0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

Indexed as

Apolipoproteins EC-Reactive ProteinHydroxymethylglutaryl-CoA Reductase InhibitorsAgedFemaleGenome-Wide Association StudyHepatocyte Nuclear Factor 1-alphaHumansMaleMiddle AgedPolymorphism, Single NucleotideWhite PeopleApoE protein, humanApolipoproteins EC-Reactive ProteinHepatocyte Nuclear Factor 1-alphaHNF1A protein, humanHydroxymethylglutaryl-CoA Reductase InhibitorsC-Reactive ProteinGWASPharmacogeneticsPharmacologyStatinsTreatment Response

Identifiers

PMID39798939
PMCPMC13222656

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.