Financiado en parte por Novo Nordisk Fonden, Novo Nordisk Foundation Center for Protein Research
Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles: a Mendelian randomization analysis
Helgadottir A, Thorleifsson G, Snaebjarnarson A, Stefansdottir L, Sveinbjornsson G, Tragante V, Björnsson E, Steinthorsdottir V, Gretarsdottir S, Helgason H, Saemundsdottir J, Olafsson I, Thune JJ, Raja AA, Ghouse J, Olesen MS, Christensen A, Jacobsen RL, Dowsett J, Bruun MT, Nielsen K, Knowlton K, Nadauld L, Benediktsson R, Erikstrup C, Pedersen OB, Banasik K, Brunak S, DBDS Genomic Consortium, Bundgaard H, Ostrowski SR, Sulem P, Arnar DO, Thorgeirsson G, Thorsteinsdottir U, Gudbjartsson DF, Stefansson K, Holm H
European journal of preventive cardiology · 29 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Gobierno
- Innovationsfonden
- Gobierno
- NordForsk
- Empresa
- Novo Nordisk Fonden
- Gobierno
- Medical Research Council
- Empresa
- Novo Nordisk Foundation Center for Protein Research
- Gobierno
- Innovation Fund Denmark
- Sin clasificar
- IFD
- Subvenciones
- Novo Nordisk Fonden (NNF20OC0066063); NordForsk (90580); Innovationsfonden (8114-00033B); Medical Research Council (MC_PC_17228); Novo Nordisk Fonden (NNF20OC0065799); Novo Nordisk Fonden (NNF18OC0031204)
Según 7 financiadores declarados.
Publicación
- Publicado
- 2022-09-19 · Eur J Prev Cardiol · vol. 29 · número 18 · págs. 2374–2385
- Editorial
- Oxford University Press
- Citado
- 30 citas · más que el 97% de estudios similares · 5.9× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 25 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology · Cholesterol and Lipid Metabolism
- Palabras clave
- apolipoprotein B, non-HDL cholesterol, coronary artery disease, atherogenic risk, genetic variants, causal inference, dyslipidemia
- MeSH
- humans, cholesterol, lipoproteins, apolipoproteins b, risk factors, atherosclerosis, cholesterol, ldl, apolipoprotein b-100, cholesterol, hdl, coronary artery disease, mendelian randomization analysis
64 autores
- Anna Helgadóttir🇮🇸 · autor de correspondenciadeCODE Genetics (Iceland)
- Guðmar Þorleifsson🇮🇸deCODE Genetics (Iceland)
- Auðunn Skúta Snæbjarnarson🇮🇸deCODE Genetics (Iceland)
- Lilja Stefánsdóttir🇮🇸deCODE Genetics (Iceland)
- Garðar Sveinbjörnsson🇮🇸deCODE Genetics (Iceland)
- Vinicius Tragante🇮🇸deCODE Genetics (Iceland)
- Eyþór Björnsson🇮🇸deCODE Genetics (Iceland)
- Valgerður Steinthórsdóttir🇮🇸deCODE Genetics (Iceland)
- Sólveig Grétarsdóttir🇮🇸deCODE Genetics (Iceland)
- Hannes Helgason🇮🇸deCODE Genetics (Iceland)
- Jona Saemundsdottir🇮🇸deCODE Genetics (Iceland)
- Ísleifur Ólafsson🇮🇸National University Hospital of Iceland
- Jens Jakob Thune🇩🇰University of Copenhagen; Bispebjerg Hospital; Copenhagen University Hospital
- Anna Axelsson Raja🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- Jonas Ghouse🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- MORTEN SALLING OLESEN🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- Alex Hørby Christensen🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- Rikke Louise Jacobsen🇩🇰Copenhagen University Hospital; Rigshospitalet
- Joseph Dowsett🇩🇰Copenhagen University Hospital; Rigshospitalet
- Mie Topholm Bruun🇩🇰Odense University Hospital
- Kaspar René Nielsen🇩🇰Aalborg University Hospital
- Kirk U. Knowlton🇺🇸Intermountain Healthcare
- Lincoln D. Nadauld🇺🇸Intermountain Healthcare
- Rafn Benediktsson🇮🇸National University Hospital of Iceland
- Christian Erikstrup🇩🇰Copenhagen Business School; Aarhus University Hospital
- Ole Birger Pedersen🇩🇰University of Copenhagen; Novo Nordisk Foundation; Zealand University Hospital Køge
- Karina Banasik🇩🇰University of Copenhagen; Novo Nordisk Foundation
- Søren Brunak🇩🇰University of Copenhagen; Novo Nordisk Foundation; Copenhagen University Hospital; Rigshospitalet
- Steffen Andersen🇩🇰Copenhagen Business School; Copenhagen University Hospital; Rigshospitalet
- Karina Banasik🇩🇰University of Copenhagen; Novo Nordisk Foundation; Aarhus University Hospital
- Søren Brunak🇩🇰University of Copenhagen; Novo Nordisk Foundation; Aarhus University Hospital
- Kristoffer Sølvsten Burgdorf🇩🇰Glostrup Hospital; Copenhagen University Hospital; Rigshospitalet
- Maria Didriksen🇩🇰Statens Serum Institut; Copenhagen University Hospital; Rigshospitalet; Danish Cancer Society
- Khoa Manh Dinh🇩🇰Aarhus University Hospital
- Christian Erikstrup🇩🇰University of Copenhagen; Aarhus University Hospital
- Daniel Fannar Gudbjartsson🇮🇸🇩🇰deCODE Genetics (Iceland); University of Iceland; Copenhagen University Hospital; Rigshospitalet
- Thomas Folkmann Hansen🇩🇰Glostrup Hospital; Copenhagen University Hospital; Rigshospitalet
- Henrik Hjalgrim🇩🇰Statens Serum Institut; Aarhus University Hospital; Danish Cancer Society
- Gregor B. E. Jemec🇩🇰Aalborg University Hospital
- Poul Jennum🇩🇰University of Copenhagen; Aarhus University
- Pär I. Johansson🇩🇰Copenhagen University Hospital; Rigshospitalet; Zealand University Hospital Køge
- Margit Anita Hørup Larsen🇩🇰Copenhagen University Hospital; Rigshospitalet; Zealand University Hospital Køge
- Susan Mikkelsen🇩🇰Aarhus University Hospital; Copenhagen University Hospital; Rigshospitalet
- Kasper Rene Nielsen🇩🇰University of Copenhagen; Aalborg University Hospital; Novo Nordisk Foundation
- Mette Nyegaard🇩🇰Statens Serum Institut; Aarhus University
- Sisse Rye Ostrowski🇩🇰University of Copenhagen; Sankt Hans Hospital; Copenhagen University Hospital; Rigshospitalet
- Ole Birger Pedersen🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; Zealand University Hospital Køge
- Kāri Stefánsson🇩🇰🇮🇸University of Copenhagen; deCODE Genetics (Iceland); University of Iceland; Copenhagen University Hospital; Rigshospitalet
- Hreinn Stefánsson🇮🇸deCODE Genetics (Iceland)
- Susanne Gjørup Sækmose🇮🇸🇩🇰deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland; Zealand University Hospital Køge
- Erik Sørensen🇮🇸🇩🇰deCODE Genetics (Iceland); University of Iceland; Copenhagen University Hospital; Rigshospitalet
- Unnur Arna Thorsteinsdottir🇮🇸deCODE Genetics (Iceland); University of Iceland
- Mie Topholm Brun🇮🇸🇩🇰deCODE Genetics (Iceland); University of Iceland; Odense University Hospital
- Henrik Ullum🇩🇰🇮🇸Statens Serum Institut; deCODE Genetics (Iceland); University of Iceland
- Thomas Mears Werge🇮🇸🇩🇰deCODE Genetics (Iceland); Sankt Hans Hospital; Copenhagen University Hospital
- Henning Bundgaard🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- Sisse Rye Ostrowski🇩🇰University of Copenhagen; Copenhagen University Hospital; Rigshospitalet
- Patrick Sulem🇮🇸deCODE Genetics (Iceland)
- Davíð O. Arnar🇮🇸deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland
- Guðmundur Þorgeirsson🇮🇸deCODE Genetics (Iceland); University of Iceland
- Unnur Arna Thorsteinsdottir🇮🇸deCODE Genetics (Iceland); University of Iceland
- Daniel Fannar Gudbjartsson🇮🇸deCODE Genetics (Iceland); University of Iceland
- Kāri Stefánsson🇮🇸deCODE Genetics (Iceland); University of Iceland
- Hilma Hólm🇮🇸deCODE Genetics (Iceland)
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background and aims
The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration.
Method and results
We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis, both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance.
Conclusion
Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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