A genome‐wide association study of multiple longitudinal traits with related subjects
Why this work is in the frame
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Bibliographic record
Abstract
Pleiotropy is a phenomenon that a single gene inflicts multiple correlated phenotypic effects, often characterized as traits, involving multiple biological systems. We propose a two-stage method to identify pleiotropic effects on multiple longitudinal traits from a family-based data set. The first stage analyzes each longitudinal trait via a three-level mixed-effects model. Random effects at the subject-level and at the family-level measure the subject-specific genetic effects and between-subjects intraclass correlations within families, respectively. The second stage performs a simultaneous association test between a single nucleotide polymorphism and all subject-specific effects for multiple longitudinal traits. This is performed using a quasi-likelihood scoring method in which the correlation structure among related subjects is adjusted. Two simulation studies for the proposed method are undertaken to assess both the type I error control and the power. Furthermore, we demonstrate the utility of the two-stage method in identifying pleiotropic genes or loci by analyzing the Genetic Analysis Workshop 16 Problem 2 cohort data drawn from the Framingham Heart Study and illustrate an example of the kind of complexity in data that can be handled by the proposed approach. We establish that our two-stage method can identify pleiotropic effects whilst accommodating varying data types in the model.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 it