The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study
Bibliographic record
Abstract
Abstract Objectives Endocrine disrupting chemicals (EDCs) interfere with hormonal homeostasis, and have been observationally linked to altered pubertal timing, defined by the age of menarche (AAM) in girls and the age at voice change (AVC) in boys. However, the causality of these associations remains unclear. We used Mendelian randomization (MR) to investigate if genetically altered serum EDC levels affect pubertal timing. Methods We performed univariate MR to assess the effects of 22 EDCs on AAM and AVC, using the largest GWAS for EDCs as well as European and multi-ethnic GWAS on AAM and AVC. Multivariate MR (MVMR) and two-step MR were conducted to examine mediating effects of body mass index (BMI). Results We found causal MR associations with AAM for three polychlorinated biphenyls (PCBs): PCB 74 (β IVW : −0.015, 95 % CI [−0.028, −0.003], p=0.014), PCB 194 (β IVW : −0.015, 95 % CI [−0.024, −0.007], p=3.27×10 −4 ), and PCB 206 (β IVW : −0.024, 95 % CI [−0.041, −0.006], p=0.0068) and for dibutyl phthalate (DBP, β IVW : 0.006, 95 % CI [0.001, 0.010], p=0.013). One MR association was found with AVC for bisphenol A (BPA, β Wald ratio = −0.032, 95 % CI [−0.044, −0.019], p=2.62×10 −7 ). Mediation analyses by MVMR or Two-Step MR suggested BMI’s mediating role in the associations of EDCs with AAM and AVC. Conclusions Our findings indicate that exposure to specific PCBs leads to earlier AAM whereas exposure to DBP delays AAM. Exposure to BPA leads to earlier AVC, with BMI potentially acting as a mediator.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".