Cumulative Meta-Analysis for Genetic Association: When Is a New Study Worthwhile?
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVES: In this paper, we address the questions: how large a sample size would be required to show genome-wide significance between a single nucleotide polymorphism (SNP) and a genetic trait in a meta-analysis of a newly planned study together with the existing ones? Or alternatively: will a planned study of size n be able to provide evidence of a genetic association when this study is combined with a current meta-analysis? METHODS: We examine the potential impact of a newly planned genetic study on an existing meta-analysis through the use of a simulation-based algorithm. The proposed approach provides an empirical estimate of the power of the updated meta-analysis to detect genome-wide significance (p<5.0×10(-8)) of a complex trait and each of a set of specific SNPs of interest or the expected p value of the updated meta-analysis including the current and proposed studies. RESULTS: This technique is illustrated in the context of an updated meta-analysis of case-control studies in Paget's disease. A second example illustrates the impact of adding a newly planned study to a large meta-analysis of SNP associations with human height. CONCLUSIONS: The proposed algorithm is particularly useful for the design of studies to assess a selected set of high-priority SNP associations that are 'nearly' significant in meta-analysis of existing studies. The results may help investigators decide whether an updated meta-analysis is likely to achieve genome-wide significance.
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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 | 0.001 | 0.000 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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