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Protein identification for stroke progression via Mendelian Randomization in Million Veteran Program and UK Biobank.
Elmore, Andrew; Adhikari, Nimish; Hartley, April E; Javier Aparicio, Hugo; Posner, Dan C; Hemani, Gibran; Tilling, Kate; Gaunt, Tom R; Wilson, Peter; Casas, J P; Michael Gaziano, John; Smith, George Davey; Paternoster, Lavinia; Cho, Kelly; Peloso, Gina M.
Afiliación
  • Elmore A; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol.
  • Adhikari N; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol.
  • Hartley AE; Veteran's Affairs Healthcare System, Boston, MA.
  • Javier Aparicio H; Department of Biostatistics, Boston University School of Public Health, Boston, MA.
  • Posner DC; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol.
  • Hemani G; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol.
  • Tilling K; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA.
  • Gaunt TR; Boston Medical Center, Boston, MA.
  • Wilson P; Veteran's Affairs Healthcare System, Boston, MA.
  • Casas JP; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol.
  • Michael Gaziano J; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol.
  • Smith GD; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol.
  • Paternoster L; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol.
  • Cho K; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol.
  • Peloso GM; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol.
medRxiv ; 2024 Feb 01.
Article en En | MEDLINE | ID: mdl-38352469
ABSTRACT

Background:

Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods:

We performed genome-wide association studies (GWAS) for subsequent major adverse cardiovascular events (MACE) (Ncases=51,929, Ncntrl=39,980) and subsequent arterial ischemic stroke (AIS) Ncases=45,120, Ncntrl=46,789) after first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (pQTLs) to determine the effect of 1,463 plasma protein abundances on subsequent MACE using Mendelian randomization (MR).

Results:

Two variants were significantly associated with subsequent cardiovascular events rs76472767 (OR=0.75, 95% CI = 0.64-0.85, p= 3.69×10-08) with subsequent AIS and rs13294166 (OR=1.52, 95% CI = 1.37-1.67, p=3.77×10-08) with subsequent MACE. Using MR, we identified 2 proteins with an effect on subsequent MACE after a stroke CCL27 (effect OR= 0.77, 95% CI = 0.66-0.88, adj. p=0.05), and TNFRSF14 (effect OR=1.42, 95% CI = 1.24-1.60, adj. p=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation.

Conclusions:

We found evidence that two proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos