Novel genetic determinants of high-density lipoprotein cholesterol (HDL-C) in the French Canadian population
Bibliographic record
Abstract
HDL-C levels, are an independent risk factor for heart disease, and are influenced by multiple genes and environmental factors. Choosing an isolated population could reduce the heterogeneity and increase power to discover susceptibility genes for low HDL-C. To identify novel genetic determinants that contribute to HDL-C levels, I used several genetic approaches on highly informative families of French Canadian descent with probands selected for HDL-C levels < 5th% (age and sex specific). The estimated heritability of HDL-C for this cohort was 0.73. Using a candidate gene approach, I identified a novel mutation of ApoAI (apo AIE136X) in three probands. Segregation analysis showed a strong co-segregation of the ApoAI allele with the low HDL-C trait in these kindreds. I also performed whole genome linkage analysis using 485 markers situated at intervals of 6 centiMorgans (cM). In parametric two-point linkage analyses, the highest two-point LOD score of 4.6 was observed with the marker D4S424 on chromosome 4q31.21. I further refined the linked region from 12.2 cM to 2.9 cM (2.37 Mb) by genotyping 15 additional markers in the three families with the highest LOD-scores. None of the genes residing in the significantly restricted 2.37 Mb region has previously been associated with HDL-C metabolism. In quantitative linkage analysis, I identified significant linkage to a locus on chromosome 16q23-24 that had been previously implicated in linkage scans for HDL-C. I examined this region for association using both family-based and case-control analyses. Within an 18.1 cM region (7.8 Mb) four families demonstrated segregation. All coding regions and exon-intron boundaries of all genes within this region were sequenced. A missense variant in the CHST6 gene showed segregation in four families. An association analysis that included all of the French Canadian families as well as other cohorts showed association for one com
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".