Genetic architecture of tuberculosis susceptibility: A comprehensive research synopsis, meta-analyses, and epidemiological evidence
Bibliographic record
Abstract
To date, many studies have been conducted to investigate associations between variants and tuberculosis risk; however, the results have been inconclusive. Here, we systematically provide a summary of the understanding of the genetic architecture of tuberculosis susceptibility. We searched PubMed, Embase and Web of Science to identify genetic association studies of tuberculosis published through October 31, 2021. We conducted meta-analyses for the genetic association with tuberculosis risk. We graded levels of cumulative epidemiological evidence of significant associations with risk of tuberculosis and false-positive report probability tests. We performed functional annotations for these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project and other databases. We identified 703 eligible articles comprising 298,074 cases and 879,593 controls through screening a total of 24,398 citations. Meta-analyses were conducted for 614 genetic variants in 469 genes or loci. We found 39 variants that were nominally significantly associated with tuberculosis risk. Cumulative epidemiological evidence for a significant association was graded strong for 9 variants in or near 9 genes. Among them, 5 variants were associated with tuberculosis risk in at least three main ethnicity (African, Asian and White) which together explained approximately 9.59% of the familial relative risk of tuberculosis. Data from ENCODE and other databases suggested that 8 of these 9 genetic variants with strong evidence might fall within putative functional regions. Our study summarizes the current literature on the genetic architecture of tuberculosis susceptibility and provides useful data for designing future studies to investigate the genetic association with tuberculosis risk.
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How this classification was reachedexpand
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) | 0.004 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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, unvalidatedMachine predicted; a candidate call from one teacher head, 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".