---
OA_place: publisher
OA_type: hybrid
_id: '18754'
abstract:
- lang: eng
  text: 'Exploring the molecular correlates of metabolic health measures may identify
    their shared and unique biological processes and pathways. Molecular proxies of
    these traits may also provide a more objective approach to their measurement.
    Here, DNA methylation (DNAm) data were used in epigenome-wide association studies
    (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits:
    body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures
    of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000
    volunteers from the Generation Scotland (GS) cohort. We observed a maximum of
    12,033 significant findings (p < 3.6 × 10−8) for BMI in a marginal linear regression
    EWAS. By contrast, a joint and conditional Bayesian penalized regression approach
    yielded 27 high-confidence associations with BMI. EpiScores trained in GS performed
    well in both Scottish and Singaporean test cohorts (Lothian Birth Cohort 1936
    [LBC1936] and Health for Life in Singapore [HELIOS]). The EpiScores for BMI and
    total cholesterol performed best in HELIOS, explaining 20.8% and 7.1% of the variance
    in the measured traits, respectively. The corresponding results in LBC1936 were
    14.4% and 3.2%, respectively. Differences were observed in HELIOS for body fat,
    where the EpiScore explained ∼9% of the variance in Chinese and Malay -subgroups
    but ∼3% in the Indian subgroup. The EpiScores also correlated with cognitive function
    in LBC1936 (standardized βrange: 0.08–0.12, false discovery rate p [pFDR] < 0.05).
    Accounting for the correlation structure across the methylome can vastly affect
    the number of lead findings in EWASs. The EpiScores of metabolic traits are broadly
    applicable across populations and can reflect differences in cognition.'
article_processing_charge: No
article_type: original
author:
- first_name: Hannah M.
  full_name: Smith, Hannah M.
  last_name: Smith
- first_name: Hong Kiat
  full_name: Ng, Hong Kiat
  last_name: Ng
- first_name: Joanna E.
  full_name: Moodie, Joanna E.
  last_name: Moodie
- first_name: Danni A.
  full_name: Gadd, Danni A.
  last_name: Gadd
- first_name: Daniel L.
  full_name: Mccartney, Daniel L.
  last_name: Mccartney
- first_name: Elena
  full_name: Bernabeu, Elena
  last_name: Bernabeu
- first_name: Archie
  full_name: Campbell, Archie
  last_name: Campbell
- first_name: Paul
  full_name: Redmond, Paul
  last_name: Redmond
- first_name: Adele
  full_name: Taylor, Adele
  last_name: Taylor
- first_name: Danielle
  full_name: Page, Danielle
  last_name: Page
- first_name: Janie
  full_name: Corley, Janie
  last_name: Corley
- first_name: Sarah E.
  full_name: Harris, Sarah E.
  last_name: Harris
- first_name: Darwin
  full_name: Tay, Darwin
  last_name: Tay
- first_name: Ian J.
  full_name: Deary, Ian J.
  last_name: Deary
- first_name: Kathryn L.
  full_name: Evans, Kathryn L.
  last_name: Evans
- first_name: Matthew Richard
  full_name: Robinson, Matthew Richard
  id: E5D42276-F5DA-11E9-8E24-6303E6697425
  last_name: Robinson
  orcid: 0000-0001-8982-8813
- first_name: John C.
  full_name: Chambers, John C.
  last_name: Chambers
- first_name: Marie
  full_name: Loh, Marie
  last_name: Loh
- first_name: Simon R.
  full_name: Cox, Simon R.
  last_name: Cox
- first_name: Riccardo E.
  full_name: Marioni, Riccardo E.
  last_name: Marioni
- first_name: Robert F.
  full_name: Hillary, Robert F.
  last_name: Hillary
citation:
  ama: Smith HM, Ng HK, Moodie JE, et al. DNA methylation-based predictors of metabolic
    traits in Scottish and Singaporean cohorts. <i>American Journal of Human Genetics</i>.
    2025;112(1):106-115. doi:<a href="https://doi.org/10.1016/j.ajhg.2024.11.012">10.1016/j.ajhg.2024.11.012</a>
  apa: Smith, H. M., Ng, H. K., Moodie, J. E., Gadd, D. A., Mccartney, D. L., Bernabeu,
    E., … Hillary, R. F. (2025). DNA methylation-based predictors of metabolic traits
    in Scottish and Singaporean cohorts. <i>American Journal of Human Genetics</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.ajhg.2024.11.012">https://doi.org/10.1016/j.ajhg.2024.11.012</a>
  chicago: Smith, Hannah M., Hong Kiat Ng, Joanna E. Moodie, Danni A. Gadd, Daniel
    L. Mccartney, Elena Bernabeu, Archie Campbell, et al. “DNA Methylation-Based Predictors
    of Metabolic Traits in Scottish and Singaporean Cohorts.” <i>American Journal
    of Human Genetics</i>. Elsevier, 2025. <a href="https://doi.org/10.1016/j.ajhg.2024.11.012">https://doi.org/10.1016/j.ajhg.2024.11.012</a>.
  ieee: H. M. Smith <i>et al.</i>, “DNA methylation-based predictors of metabolic
    traits in Scottish and Singaporean cohorts,” <i>American Journal of Human Genetics</i>,
    vol. 112, no. 1. Elsevier, pp. 106–115, 2025.
  ista: Smith HM, Ng HK, Moodie JE, Gadd DA, Mccartney DL, Bernabeu E, Campbell A,
    Redmond P, Taylor A, Page D, Corley J, Harris SE, Tay D, Deary IJ, Evans KL, Robinson
    MR, Chambers JC, Loh M, Cox SR, Marioni RE, Hillary RF. 2025. DNA methylation-based
    predictors of metabolic traits in Scottish and Singaporean cohorts. American Journal
    of Human Genetics. 112(1), 106–115.
  mla: Smith, Hannah M., et al. “DNA Methylation-Based Predictors of Metabolic Traits
    in Scottish and Singaporean Cohorts.” <i>American Journal of Human Genetics</i>,
    vol. 112, no. 1, Elsevier, 2025, pp. 106–15, doi:<a href="https://doi.org/10.1016/j.ajhg.2024.11.012">10.1016/j.ajhg.2024.11.012</a>.
  short: H.M. Smith, H.K. Ng, J.E. Moodie, D.A. Gadd, D.L. Mccartney, E. Bernabeu,
    A. Campbell, P. Redmond, A. Taylor, D. Page, J. Corley, S.E. Harris, D. Tay, I.J.
    Deary, K.L. Evans, M.R. Robinson, J.C. Chambers, M. Loh, S.R. Cox, R.E. Marioni,
    R.F. Hillary, American Journal of Human Genetics 112 (2025) 106–115.
date_created: 2025-01-05T23:01:56Z
date_published: 2025-01-02T00:00:00Z
date_updated: 2025-02-27T12:38:23Z
day: '02'
ddc:
- '570'
department:
- _id: MaRo
doi: 10.1016/j.ajhg.2024.11.012
external_id:
  isi:
  - '001412498600001'
  pmid:
  - '39706196'
file:
- access_level: open_access
  checksum: 891d120554f07da2c35d38388c29a690
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-08T09:26:42Z
  date_updated: 2025-01-08T09:26:42Z
  file_id: '18776'
  file_name: 2025_AJHG_Smith.pdf
  file_size: 2266488
  relation: main_file
  success: 1
file_date_updated: 2025-01-08T09:26:42Z
has_accepted_license: '1'
intvolume: '       112'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 106-115
pmid: 1
publication: American Journal of Human Genetics
publication_identifier:
  eissn:
  - 1537-6605
  issn:
  - 0002-9297
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/marioni-group/Metabolic_trait
scopus_import: '1'
status: public
title: DNA methylation-based predictors of metabolic traits in Scottish and Singaporean
  cohorts
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2025'
...