DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain
Year: 2023
Type: preprint
Study design: Observational Study
Abstract: Background Plasma growth differentiation factor 15 (GDF15) and N-terminal pro-B-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 that 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 <0.03). 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.
Source: medRxiv
Authors: 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 Russ, Sarah E. Harris, Paul Welsh, Naveed Sattar, Simon R. Cox, Daniel L. McCartney, Riccardo E. Marioni
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Translational Neuroscience - training the next generation of basic neuroscientists to embrace clinical research., Factors of biological ageing: does it all go together when it goes?, G259633682, Stratifying Resilience and Depression Longitudinally (STRADL), Translational Neuroscience 2 (TN2), G6868616705, Translational Neuroscience 2 (TN2), G9000063527
OpenAlex ID: W4387770303