GENETIC LOCI INFLUENCING C-REACTIVE PROTEIN LEVELS AND CORONARY HEART DISEASE RISK: RESULTS OF GENETIC ASSOCIATION AND MENDELIAN RANDOMISATION STUDY WITH META-ANALYSIS IN 80 614 PEOPLE
Bibliographic record
Abstract
Background Plasma levels of C-reactive protein (CRP) are independently associated with the risk of coronary heart disease (CHD). Whether the relationship of CRP with CHD is causal, or whether CRP is simply an “innocent bystander” of the inflammatory disease process, is unknown. Methods We first carried out a genome-wide association (n = 17 967) and replication study (n = 14 747) to identify genetic loci associated with plasma CRP concentrations. At each locus, we selected the most closely associated (“top-ranking”) single nucleotide polymorphism (SNP) for testing against CHD. For the CRP locus, we then carried out a Mendelian randomisation experiment and meta-analysis with published studies, providing data for 21 876 cases and 58 738 controls. Results Genetic variants in the CRP, LEPR, IL-6R, HNF1A and APOE-CI-CII loci were strongly associated with differences in CRP levels. Polymorphisms in LEPR (rs6700896), IL-6R (rs4537545) and APOE-CI-CII (rs4420638) were associated with the risk of CHD (p<0.002 and p<0.001). The associations between rs7553007 and other variants in the CRP locus with CHD risk were weak and non-significant. Interpretation The weak association between variants in the CRP locus and CHD risk suggests that any causal association of CRP with atherosclerosis is likely to be small. We identify LEPR and IL-6R as putative new susceptibility loci for CHD.
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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 | 0.022 | 0.032 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.008 | 0.027 |
| Bibliometrics | 0.002 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".