Polychlorinated Biphenyls (PCBs) and Parkinson's Disease (PD): Effect Modification by Membrane Transporter Variants (S32.004)
Bibliographic record
Abstract
Objective: Determine associations of PD with PCBs and investigate modification by variants in the xenobiotic-efflux membrane transporter p-glycoprotein gene (ABCB1, p-gp, MDR1) Background: PCBs have been inconsistently associated with PD risk. We recently reported significantly increased risk associated with higher serum PCBs in an Alaska Native population and much stronger associations in persons with ABCB1 variants. Here we investigate those associations in another population. Methods: We recruited people with PD (PwPD) and matched controls from the Agricultural Health Study cohort of pesticide applicators and their spouses. PD was confirmed by expert consensus. We genotyped ABCB1 single nucleotide polymorphisms (SNPs) using an Illumina custom array, and measured 15 PCB-congeners in serum using GC-MS. We adjusted for total lipid and used β-substitution to impute undetectable values, and also analyzed summed levels of PCB-118, 138, 153 and 180 (PCB_sum). We assessed associations with PD using logistic regression adjusting for age, gender and state, and examined multiplicative interactions of PCBs and SNPs. Results: Analyses included 97 PwPD and 113 controls. All PCBs were higher in PwPD. For PCB_Sum, compared with the lowest quartile (Q1), odds ratios for Q2, Q3 and Q4 were 1.7, 2.5 and 2.7, respectively (p-trend 0.02). ABCB1 coding variant rs9282564 modified PD-PCB associations: relative to those with below-median PCB_sum, above-median PCB_sum was associated with 1.4-fold (95[percnt]CI 0.7-2.8) greater risk in those with AA genotype, but 11.4-fold (95[percnt]CI 2.8-45) greater risk in those with AG or GG genotype (p-interaction 0.008). Conclusions: In this primarily Caucasian population, as in the Alaska Native population, PCB levels were higher in PwPD than controls. Risk was markedly increased in persons with both above median PCB levels and variants in ABCB1, suggesting a gene-environment interaction. Study Supported by: NIEHS-R01-ES10803, NIH Intramural Research Program (NIEHS-Z01-ES044007, Z01-ES049030; NCI-Z01-CP010119), Michael J. Fox Foundation, James and Sharron Clark.
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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) | 0.003 | 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".