---
res:
  bibo_abstract:
  - "Background: DNA methylation (DNAm) can regulate gene expression, and its genome-wide
    patterns (epigenetic scores or EpiScores) can act as biomarkers for complex traits.
    The relative stability of methylation profiles may enable better assessment of
    chronic exposures compared to single time-point protein measures. We present the
    first large-scale epigenetic study of the highly-abundant serum proteome measured
    via ultra-high throughput mass spectrometry in 14,671 samples from the Generation
    Scotland cohort. We further demonstrate the first large-scale comparison of protein
    EpiScores and their respective proteins as predictors of incident cardiovascular
    disease.\r\n\r\nResults: Marginal epigenome-wide association models, adjusting
    for age, sex, measurement batch, estimated white cell proportions, BMI, smoking
    and methylation principal components, reveal 15,855 significant CpG – protein
    associations across 125 of 133 proteins PBonferroni < 2.71 × 10-10. Bayesian epigenome-wide
    association studies of the same 133 proteins reveal 697 CpG-Protein associations
    (posterior inclusion probability > 0.95). 112 protein EpiScores correlate significantly
    with their respective protein in a holdout test-set. Of these, sixteen associate
    significantly with incident all-cause cardiovascular disease (Nevents=191) compared
    to one measured protein.\r\n\r\nConclusions: We highlight a complex interplay
    between the blood-based methylome and proteome. Importantly, we show that protein
    EpiScores correlate with measured proteins and demonstrate that the, as-yet understudied,
    high-abundance proteome may yield clinically relevant biomarkers. The protein
    EpiScores demonstrate more significant associations with cardiovascular disease
    than directly measured proteins, suggesting their potential as clinical biomarkers
    for monitoring or predicting disease risk. We suggest that biomarker development
    could be enhanced by the consideration of protein EpiScores alongside measured
    proteins.@eng"
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Josephine A.
      foaf_name: Robertson, Josephine A.
      foaf_surname: Robertson
  - foaf_Person:
      foaf_givenName: Jakub
      foaf_name: Bajzik, Jakub
      foaf_surname: Bajzik
      foaf_workInfoHomepage: http://www.librecat.org/personId=b995e25b-8c4b-11ed-a6d8-f71b7bcd6122
  - foaf_Person:
      foaf_givenName: Spyros
      foaf_name: Vernardis, Spyros
      foaf_surname: Vernardis
  - foaf_Person:
      foaf_givenName: Aleksandra D.
      foaf_name: Chybowska, Aleksandra D.
      foaf_surname: Chybowska
  - foaf_Person:
      foaf_givenName: Daniel L.
      foaf_name: Mccartney, Daniel L.
      foaf_surname: Mccartney
  - foaf_Person:
      foaf_givenName: Arturas
      foaf_name: Grauslys, Arturas
      foaf_surname: Grauslys
  - foaf_Person:
      foaf_givenName: Jure
      foaf_name: Mur, Jure
      foaf_surname: Mur
  - foaf_Person:
      foaf_givenName: Hannah M.
      foaf_name: Smith, Hannah M.
      foaf_surname: Smith
  - foaf_Person:
      foaf_givenName: Archie
      foaf_name: Campbell, Archie
      foaf_surname: Campbell
  - foaf_Person:
      foaf_givenName: Camilla
      foaf_name: Drake, Camilla
      foaf_surname: Drake
  - foaf_Person:
      foaf_givenName: Hannah
      foaf_name: Grant, Hannah
      foaf_surname: Grant
  - foaf_Person:
      foaf_givenName: Jamie
      foaf_name: Pearce, Jamie
      foaf_surname: Pearce
  - foaf_Person:
      foaf_givenName: Tom C.
      foaf_name: Russ, Tom C.
      foaf_surname: Russ
  - foaf_Person:
      foaf_givenName: Poppy
      foaf_name: Adkin, Poppy
      foaf_surname: Adkin
  - foaf_Person:
      foaf_givenName: Matthew
      foaf_name: White, Matthew
      foaf_surname: White
  - foaf_Person:
      foaf_givenName: Charles
      foaf_name: Brigden, Charles
      foaf_surname: Brigden
  - foaf_Person:
      foaf_givenName: Christoph B.
      foaf_name: Messner, Christoph B.
      foaf_surname: Messner
  - foaf_Person:
      foaf_givenName: David J.
      foaf_name: Porteous, David J.
      foaf_surname: Porteous
  - foaf_Person:
      foaf_givenName: Caroline
      foaf_name: Hayward, Caroline
      foaf_surname: Hayward
  - foaf_Person:
      foaf_givenName: Simon R.
      foaf_name: Cox, Simon R.
      foaf_surname: Cox
  - foaf_Person:
      foaf_givenName: Aleksej
      foaf_name: Zelezniak, Aleksej
      foaf_surname: Zelezniak
  - foaf_Person:
      foaf_givenName: Markus
      foaf_name: Ralser, Markus
      foaf_surname: Ralser
  - foaf_Person:
      foaf_givenName: Matthew Richard
      foaf_name: Robinson, Matthew Richard
      foaf_surname: Robinson
      foaf_workInfoHomepage: http://www.librecat.org/personId=E5D42276-F5DA-11E9-8E24-6303E6697425
    orcid: 0000-0001-8982-8813
  - foaf_Person:
      foaf_givenName: Riccardo E.
      foaf_name: Marioni, Riccardo E.
      foaf_surname: Marioni
  bibo_doi: 10.1186/s13059-025-03892-0
  bibo_volume: 26
  dct_date: 2025^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/1474-7596
  - http://id.crossref.org/issn/1474-760X
  dct_language: eng
  dct_publisher: Springer Nature@
  dct_title: Methylome-wide association studies and epigenetic biomarker development
    for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland
    participants@
  fabio_hasPubmedId: '41361833'
...