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DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.
Gadd, Danni A; Smith, Hannah M; Mullin, Donncha; Chybowska, Ola; Hillary, Robert F; Kimenai, Dorien M; Bernabeu, Elena; Cheng, Yipeng; Fawns-Ritchie, Chloe; Campbell, Archie; Page, Danielle; Taylor, Adele; Corley, Janie; Del C Valdés-Hernández, Maria; Maniega, Susana Muñoz; Bastin, Mark E; Wardlaw, Joanna M; Walker, Rosie M; Evans, Kathryn L; McIntosh, Andrew M; Hayward, Caroline; Russ, Tom C; Harris, Sarah E; Welsh, Paul; Sattar, Naveed; Cox, Simon R; McCartney, Daniel L; Marioni, Riccardo E.
Afiliación
  • Gadd DA; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Smith HM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Mullin D; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
  • Chybowska O; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
  • Hillary RF; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Kimenai DM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Bernabeu E; BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
  • Cheng Y; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Fawns-Ritchie C; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Campbell A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Page D; Division of Psychology, University of Dundee, Dundee, Scotland, UK.
  • Taylor A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • Corley J; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Del C Valdés-Hernández M; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Maniega SM; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Bastin ME; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Wardlaw JM; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.
  • Walker RM; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
  • Evans KL; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • McIntosh AM; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.
  • Hayward C; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
  • Russ TC; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Harris SE; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.
  • Welsh P; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
  • Sattar N; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Cox SR; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.
  • McCartney DL; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
  • Marioni RE; Neurovascular Imaging Research Core, UCLA, Los Angeles, CA, USA.
Clin Epigenetics ; 16(1): 124, 2024 Sep 10.
Article en En | MEDLINE | ID: mdl-39256775
ABSTRACT

BACKGROUND:

Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

RESULTS:

In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36-1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population.

CONCLUSIONS:

EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Biomarcadores / Metilación de ADN / Péptido Natriurético Encefálico / Diabetes Mellitus Tipo 2 / Factor 15 de Diferenciación de Crecimiento Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Biomarcadores / Metilación de ADN / Péptido Natriurético Encefálico / Diabetes Mellitus Tipo 2 / Factor 15 de Diferenciación de Crecimiento Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article Pais de publicación: Alemania