Abstract 4142270: Epigenetics of Shared and Unique Pathways Associated with Atherogenic Lipoprotein Particle Content and Number Across the Early Adult Life Course
Bibliographic record
Abstract
Intro: Exposure to atherogenic lipoproteins is a central determinant of atherosclerotic cardiovascular disease (ASCVD) events. Shared and unique biological pathways influence lipoprotein particle content (non-HDL-C, LDL-C) and number (apoB, LDL-P), but significant unexplained variance in blood lipoprotein levels remains. Understanding the associations between lipoprotein particle number, content, and repeated DNA methylation (DNAm) measures may provide novel insights into lipoprotein level determinants. Methods: We included 2962 participants from the Coronary Artery Risk Development in Young Adults study that had DNAm, LDL-C, non-HDL-C, apoB, and LDL-P measurements at exam years 15, 20, 25, and 30. Non-HDL-C and LDL-C were determined using standard laboratory technique. LDL particle number (LDL-P) and apoB were measured using NMR. DNAm was assessed using the Illumina Epic Array. We used separate mixed linear models adjusted for age, sex, race, and technical variables to quantify associations between DNAm sites and non-HDL-C, LDL-C, LDL-P, and apoB. We performed pathway analysis of DNAm located in gene promoter regions. We estimated % variance in lipid levels explained by associated DNAm sites using ANOVA. Results: There were 127, 182, 40, and 110 DNAm sites that were uniquely associated with LDL-C, non-HDL-C, LDL-P, and apoB, respectively. There were 114 DNAm sites associated with 3 or more of these atherogenic lipid measures. Of note, 6 DNAm sites were in the promoter of LDLR. Shared pathways included cholesterol and fatty acid metabolism, steroid and alcohol biosynthesis, as well as cellular protein transport (Table).Unique pathways generally included cholesterol synthesis for LDL-C, and energy metabolism, inflammation, and calcium transport for apoB and LDL-P. In total, identified CpGs in circulating blood leukocytes explained 14%, 24%, 16%, and 17% variance in LDL-C, non-HDL-C, LDL-P, and apoB, respectively. Conclusions: Assessment of longitudinal epigenetic patterns in peripheral leukocytes suggest unique and shared pathways mediate a large % variance in atherogenic lipids. Further exploration of the function of these DNAm sites may enhance mechanistic insight into the determinants of atherogenic lipid exposure.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".