DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

Autor: 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.; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK., Chybowska O; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, 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; BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Bernabeu E; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, 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.; Division of Psychology, University of Dundee, Dundee, Scotland, UK., Campbell A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Page D; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK., Taylor A; Department of Psychology, Lothian Birth Cohorts, 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.; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK., Maniega SM; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK., Bastin ME; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK., Wardlaw JM; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.; Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK.; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.; Neurovascular Imaging Research Core, UCLA, Los Angeles, CA, USA., Walker RM; Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.; School of Psychology, University of Exeter, Perry Road, Exeter, UK., Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., McIntosh AM; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK., Hayward C; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.; Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Russ TC; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK., Harris SE; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK., Welsh P; School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, UK., Sattar N; School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, UK., Cox SR; Department of Psychology, Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK., McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Marioni RE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. riccardo.marioni@ed.ac.uk.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2024 Sep 10; Vol. 16 (1), pp. 124. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1186/s13148-024-01734-7
Abstrakt: 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 P FDR  < 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, P FDR  < 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 (R 2 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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