DNA methylation scores were trained on 953 circulating plasma protein levels in the KORA and LBC1936 cohorts. There were 109 EpiScores selected based on performance (r > 0.1, p < 0.05) in …
Test set correlation coefficients for associations between protein EpiScores for (a) inflammatory Olink, (b) neurology Olink, and (c) SOMAmer protein panel EpiScores and measured protein levels are …
Correlation heatmap for EpiScore measures projected into Generation Scotland (N = 9537) for the 109 protein EpiScores selected in the test sample (r > 0.1, p < 0.05). At the top of the heatmap, an …
Genes selected for pathway enrichment (false discovery rate [FDR]-adjusted p < 0.05) are summarised, with the proportion of overlapping genes enriched in the gene-set also shown. The corresponding …
Mixed effects Cox proportional hazards analyses in Generation Scotland (n = 9537) tested the relationships between each of the 109 selected EpiScores and the incidence of 12 leading causes of …
Heatmap of Pearson's correlations (r) between the 70 protein EpiScore measures that were associated with incident disease (with p < 0.05 in the fully adjusted Cox mixed effects proportional hazards …
EpiScore-disease associations for 9 of the 11 morbidities with associations where p < 0.05 in the fully adjusted mixed effects Cox proportional hazards models in Generation Scotland (n = 9537). …
EpiScores with a minimum of three relationships with incident morbidities in the fully adjusted Cox models. The network includes 16 EpiScores as dark blue (SOMAscan) and grey (Olink) nodes, with …
EpiScore-incident diabetes associations in Generation Scotland (n = 9537). The 34 SOMAscan (top panel) and four Olink (bottom panel) associations shown with p < 0.05 in fully adjusted mixed effects …
Counts are provided for the number of cases and controls for each incident trait in the basic and fully adjusted Cox models run in the Generation Scotland cohort (n = 9537). Mean time-to-event is …
Basic model | Fully adjusted model | |||||
---|---|---|---|---|---|---|
Morbidity | N cases | N controls | Years to event (mean, SD) | N cases | N controls | Years to event (mean, SD) |
Rheumatoid arthritis | 63 | 9289 | 5.6 (3.5) | 52 | 7742 | 6.1 (3.3) |
Alzheimer’s dementia | 69 | 3764 | 7.7 (3) | 52 | 3137 | 7.6 (3.1) |
Bowel cancer | 78 | 9398 | 6.4 (3.2) | 66 | 7817 | 6.5 (3.2) |
Depression | 95 | 8317 | 4 (3.2) | 75 | 6984 | 3.8 (3.2) |
Lung cancer | 100 | 9433 | 5.6 (3.2) | 78 | 7850 | 5.6 (3.1) |
Breast cancer | 131 | 5356 | 6.1 (3.4) | 111 | 4402 | 5.9 (3.4) |
Inflammatory bowel disease | 194 | 9114 | 5 (3.6) | 155 | 7592 | 4.8 (3.6) |
Stroke | 313 | 9026 | 6.4 (3.4) | 246 | 7547 | 6.3 (3.5) |
COPD | 322 | 8960 | 5.5 (3.4) | 253 | 7476 | 5.5 (3.5) |
Ischaemic heart disease | 385 | 8649 | 5.6 (3.4) | 302 | 7251 | 5.7 (3.4) |
Diabetes | 429 | 8757 | 5.6 (3.4) | 322 | 7332 | 5.5 (3.4) |
Pain | 1329 | 5480 | 4.8 (3.5) | 1081 | 4593 | 4.9 (3.5) |
COPD: chronic obstructive pulmonary disease.
Demographic information and supplementary datasets.
(A) Demographic and array information for the cohorts and samples used in the study. (B) SomaScan panel EpiScore performance in the Stratifying Resilience and Depression Longitudinally (STRADL) test set. (C) Performance of Olink panel EpiScores in holdout, STRADL, and LBC1921 test sets. (D) Annotations for the proteins corresponding to the 109 selected EpiScores. (E) Predictor weights for the 109 EpiScores from Olink and SomaScan panels which passed testing in independent cohorts. (F) CpG feature counts for the 109 selected EpiScores. (G) Frequency of CpG sites selected for EpiScores with EWAS catalog annotations to phenotypic traits. (H) FUMA canonical pathway Gene set enrichment for the genes encoding the 109 proteins EpiScores were trained on. (I) Basic Cox proportional hazards model results in Generation Scotland. (J) Fully adjusted and sensitivity analyses results for Cox proportional hazards models in Generation Scotland. (K) Schoenfeld residual Cox sensitivity analyses. (L) Schoenfeld residual Cox sensitivity analyses split by year of follow-up. (M) SOMAscan-EpiScore diabetes association lookup against three large-scale plasma protein-diabetes studies. (N) White blood cell sensitivity analyses. (O) GrimAge sensitivity analyses. (P) COVID-19 analyses. Q-1B1 Primary and secondary diagnosis codes for each of the 12 morbidities in this study that were used to assign case/control status of participants.