Oral Presentation GENEMAPPERS 2026

An epigenome-wide association study of GDF15 in a multi-ethnic acute coronary syndromes cohort (#8)

Samuel FP Gibbs 1 , Gregory T Jones 2 , Anna P Pilbrow 1 , Vicky A Cameron 1 , Chris M Frampton 1 , Allamanda F Faatoese 1 , Nikki J Earle 3 , Katrina K Poppe 3 , Anna Rolleston 4 , Robert N Doughty 3 5
  1. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
  2. Department of Surgical Sciences, University of Otago, Dunedin, New Zealand
  3. Department of Medicine, University of Auckland, Auckland, New Zealand
  4. Centre for Health, Tauranga, New Zealand
  5. Greenlane Cardiovascular Service, Te Toka Tumai Auckland Hospital, Auckland, New Zealand

Background: Circulating concentrations of growth differentiation factor 15 (GDF15) are elevated in times of acute cardiac stress. Here we report an epigenome-wide association study (EWAS) of GDF15 in the Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS).

Methods: MENZACS enrolled participants admitted with first-time acute coronary syndromes (ACS) from 10 NZ hospitals between 2015 and 2024. Whole-blood DNA methylation (DNAm) was measured using Illumina MethylationEPIC v1 or v2  arrays. The EPIC v1 group was randomly partitioned into training (90%) and test (10%) datasets. In the training set, an EWAS for GDF15 adjusted for age, sex, ethnicity and blood cell composition was performed. Significant CpG sites were used to train a predictor of GDF15 using elastic net regression with 10-fold cross validation. The predictor was projected into the test and EPIC v2 datasets. A previous epigenetic predictor of GDF15[1] was calculated for comparison. Variance explained (R2) was estimated by regressing measured GDF15 on each epigenetic score.

Results: For 1038 participants with GDF15 and DNAm data available, mean age was 57 years. 30% were female, 53% were NZ European, 28% were Māori, 10% were Pacific, and 8% were Indian. Median GDF15 was 1186 (interquartile range, 852, 1730) pg/mL. In the training dataset (n=867, 82%), EWAS identified 459 CpG sites (p<3.6x10-8). The epigenetic score explained 24% of variation in GDF15 levels in the test dataset (n=96, 9%) and 26% in the EPIC v2 group (n=75, 9%). The published epigenetic score explained 12% GDF15 variation in the test group and 17% in the EPIC v2 group. In Māori and Pacific participants of the EPIC v2 group (n=48), the MENZACS derived score explained 33% variation in GDF15.

Discussion: GDF15 levels are associated with DNAm in people with ACS. Tailoring epigenetic scores to disease contexts and increasing diversity within training samples and may improve accuracy.

  1. 1. Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Assimes TL, Ferrucci L, Horvath S. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-27.