Optimum Study Design for Detecting Imprinting and Maternal Effects Based on Partial Likelihood
Bibliographic record
Abstract
Despite spectacular advances in molecular genomic technologies in the past two decades, resources available for genomic studies are still finite and limited, especially for family-based studies. Hence, it is important to consider an optimum study design to maximally utilize limited resources to increase statistical power in family-based studies. A particular question of interest is whether it is more profitable to genotype siblings of probands or to recruit more independent families. Numerous studies have attempted to address this study design issue for simultaneous detection of imprinting and maternal effects, two important epigenetic factors for studying complex diseases. The question is far from settled, however, mainly due to the fact that results and recommendations in the literature are based on anecdotal evidence from limited simulation studies rather than based on rigorous statistical analysis. In this article, we propose a systematic approach to study various designs based on a partial likelihood formulation. We derive the asymptotic properties and obtain formulas for computing the information contents of study designs being considered. Our results show that, for a common disease, recruiting additional siblings is beneficial because both affected and unaffected individuals will be included. However, if a disease is rare, then any additional siblings recruited are most likely to be unaffected, thus contributing little additional information; in such cases, additional families will be a better choice with a fixed amount of resources. Our work thus offers a practical strategy for investigators to select the optimum study design within a case-control family scheme before data collection.
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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 | 0.153 | 0.293 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.002 | 0.004 |
| Open science | 0.003 | 0.004 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".