Comparing baseline and longitudinal measures in association studies
Bibliographic record
Abstract
In recent years, longitudinal family-based studies have had success in identifying genetic variants that influence complex traits in genome-wide association studies. In this paper, we suggest that longitudinal analyses may contain valuable information that can enable identification of additional associations compared to baseline analyses. Using Genetic Analysis Workshop 18 data, consisting of whole genome sequence data in a pedigree-based sample, we compared 3 methods for the genetic analysis of longitudinal data to an analysis that used baseline data only. These longitudinal methods were (a) longitudinal mixed-effects model; (b) analysis of the mean trait over time; and (c) a 2-stage analysis, with estimation of a random intercept in the first stage and regression of the random intercept on a single-nucleotide polymorphism at the second stage. All methods accounted for the familial correlation among subjects within a pedigree. The analyses considered common variants with minor allele frequency above 5% on chromosome 3. Analyses were performed without knowledge of the simulation model. The 3 longitudinal methods showed consistent results, which were generally different from those found by using only the baseline observation. The gene CACNA2D3, identified by both longitudinal and baseline approaches, had a stronger signal in the longitudinal analysis (p = 2.65 × 10(-7)) compared to that in the baseline analysis (p = 2.48 × 10(-5)). The effect size of the longitudinal mixed-effects model and mean trait were higher compared to the 2-stage approach. The longitudinal results provided stable results different from that using 1 observation at baseline and generally had lower p values.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.156 | 0.295 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.004 | 0.006 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.003 | 0.004 |
| Open science | 0.003 | 0.004 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".