Genetic and secondary causes of severe HDL deficiency and cardiovascular disease
Bibliographic record
Abstract
Supplementary key words apoA-I ABCA1 lecithin:cholesterol acyltransferase lipoprotein lipase high density lipoprotein metabolism reverse cholesterol metabolism dyslipidemia genes in lipid disorders It has been concluded that genetic HDL deficiency is not causative for atherosclerotic cardiovascular disease (ASCVD), in contrast to genetic hypercholesterolemia associated with elevated levels of LDL cholesterol (LDL-C) or genetic hypertriglyceridemia (1, 2). This assessment has been reported in high-impact journals by a very large number of authors, representing some of the most prominent and well-known scientists in our field. The data generated stem from a very large number of subjects studied with and without ASCVD. The analyses, however, were based entirely on SNPs, mainly in intronic DNA regions, and excluded the four most important genes that regulate HDL cholesterol (HDL-C) levels: ABCA1, LCAT, APOA1, and LPL. The exclusions were justified by study findings that 1) genetic variations at the ABCA1, LCAT, APOA1, and LPL gene loci also affect TG and/or LDL-C levels and 2) an LIPC variant was not associated with ASCVD (1, In our view this justification is flawed. Our recent review of severe HDL deficiency has documented that patients with HDL-C levels <20 mg/dl in the absence of secondary causes may have premature ASCVD, especially if such patients are homozygous or compound heterozygous for mutations in the APOA1 or ABCA1 genes (3).
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".