Gene‐based association analysis of survival traits via functional regression‐based mixed effect cox models for related samples
Bibliographic record
Abstract
The importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests. In this paper, we extend this approach to analyze censored traits for family data or related samples using FR based mixed effect Cox models (FamCoxME). The FamCoxME model effect of major gene as fixed mean via functional data analysis techniques, the local gene or polygene variations or both as random, and the correlation of pedigree members by kinship coefficients or genetic relationship matrix or both. The association between the censored trait and the major gene is tested by likelihood ratio tests (FamCoxME FR LRT). Simulation results indicate that the LRT control the type I error rates accurately/conservatively and have good power levels when both local gene or polygene variations are modeled. The proposed methods were applied to analyze a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). The FamCoxME provides a new tool for gene-based analysis of family-based studies or related samples.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Methods About the Canadian research system: no · About a Canadian topic: no | Simulation or modeling | high |
| gpt | no category Domain: not available · Genre: Methods About the Canadian research system: no · About a Canadian topic: no | Other design | medium |
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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 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, unvalidatedLabeled directly by 2 models reading the full record.
The models disagree on parts of this classification; every voice is preserved in the section at the end of the page.
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".