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

Danni A. Gadd; Hannah M. Smith; Donncha Mullin; Ola Chybowska; Robert F. Hillary; Dorien M. Kimenai; Elena Bernabeu; Yipeng Cheng; Chloe Fawns-Ritchie; Archie Campbell; Danielle Page; Adele Taylor; Janie Corley; Maria Del C. Valdés-Hernández; Susana Muñoz Maniega; Mark E. Bastin; Joanna M. Wardlaw; Rosie M. Walker; Kathryn L. Evans; Andrew M. McIntosh; Caroline Hayward; Tom C. Russ; Sarah E. Harris; Paul Welsh; Naveed Sattar; Simon R. Cox; Daniel L. McCartney; Riccardo E. Marioni

doi:10.1186/s13148-024-01734-7

Clinical Epigenetics (Sep 2024)

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

Danni A. Gadd,
Hannah M. Smith,
Donncha Mullin,
Ola Chybowska,
Robert F. Hillary,
Dorien M. Kimenai,
Elena Bernabeu,
Yipeng Cheng,
Chloe Fawns-Ritchie,
Archie Campbell,
Danielle Page,
Adele Taylor,
Janie Corley,
Maria Del C. Valdés-Hernández,
Susana Muñoz Maniega,
Mark E. Bastin,
Joanna M. Wardlaw,
Rosie M. Walker,
Kathryn L. Evans,
Andrew M. McIntosh,
Caroline Hayward,
Tom C. Russ,
Sarah E. Harris,
Paul Welsh,
Naveed Sattar,
Simon R. Cox,
Daniel L. McCartney,
Riccardo E. Marioni

Affiliations

Danni A. Gadd: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Hannah M. Smith: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Donncha Mullin: Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh
Ola Chybowska: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Robert F. Hillary: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Dorien M. Kimenai: BHF Centre for Cardiovascular Science, University of Edinburgh
Elena Bernabeu: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Yipeng Cheng: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Chloe Fawns-Ritchie: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Archie Campbell: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Danielle Page: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Adele Taylor: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Janie Corley: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Maria Del C. Valdés-Hernández: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Susana Muñoz Maniega: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Mark E. Bastin: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Joanna M. Wardlaw: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Rosie M. Walker: Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh
Kathryn L. Evans: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Andrew M. McIntosh: Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh
Caroline Hayward: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Tom C. Russ: Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh
Sarah E. Harris: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Paul Welsh: School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, University of Glasgow
Naveed Sattar: School of Cardiovascular and Metabolic Health, BHF Glasgow Cardiovascular Research Centre, University of Glasgow
Simon R. Cox: Department of Psychology, Lothian Birth Cohorts, University of Edinburgh
Daniel L. McCartney: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh
Riccardo E. Marioni: Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh

DOI: https://doi.org/10.1186/s13148-024-01734-7
Journal volume & issue: Vol. 16, no. 1
pp. 1 – 15

Abstract

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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 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 (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.

Published in Clinical Epigenetics

ISSN: 1868-7083 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General): Genetics
Website: https://clinicalepigeneticsjournal.biomedcentral.com/

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