Abstract P240: Higher Body Mass Index is Associated With Lower Placental Expression of EPYC: Results From a Genome-Wide Transcriptomic Study in the Gen3G Cohort
Bibliographic record
Abstract
Background: Elevated maternal body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. Identification of alterations in the placental transcriptome may elucidate molecular markers of the biological pathways underlying these associations. Methods: We investigated the association of first trimester maternal BMI with the placental transcriptome in Gen3G, a large population-based pregnancy cohort. We completed RNA sequencing of 449 placental samples and performed differential gene expression analysis of over 15,000 genes (Limma Voom). We used maternal BMI as a continuous variable, with estimates reported as change in normalized gene expression per 1-unit increase in BMI (kg/m2), as well as a categorical variable (participants with normal weight (N=270) vs. obesity (N=82)), with RNA expression estimates reported as log2 fold changes. We adjusted models for maternal age, fetal sex, gestational age and 6 surrogate variables inferred from the expression data to adjust for batch effects and other unmeasured sources of variability. We accounted for multiple testing using False Discovery Rate (FDR). Sensitivity analyses were performed by removing cases of gestational diabetes and hypertensive disorders in pregnancy. Results: At enrollment in early pregnancy, participants had a mean ± SD age of 28.2 ± 4.4 years and measured BMI of 25.4 ± 5.5 kg/m 2 ; 57% of participants were categorized in normal weight, 22% in overweight and 18% in obesity BMI categories. Maternal BMI was significantly associated with decreased expression of EPYC , a gene that regulates fibrillogenesis (slope= -0.14, FDR-adjusted P=1.68x10 -5 for continuous BMI; log2 fold change= -1.71, FDR-adjusted P=1.06x10 -2 for obesity vs. normal weight). Both sensitivity analyses with the removal of gestational diabetes and hypertensive disorders revealed similar associations for EPYC . Conclusions: We identified an association between elevated maternal BMI and downregulation of EPYC expression in the placenta. Additional studies are required to examine the role of placental EPYC expression in maternal and fetal health.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".