Abstract 2414: Genome-wide Association Analyses From The Vitamin Intervention For Stroke Prevention (visp) Trial Identify Genetic Loci That Influence Post-stroke Measures Of Inflammation And Thrombosis
Bibliographic record
Abstract
The Vitamin Intervention for Stroke Prevention (VISP) trial was a multi-center, controlled, double blinded clinical trial, designed to determine whether the daily intake of high dose folic acid, vitamins B 6 and B 12 reduced recurrent cerebral infarction. As part of GARNET (the Genomics and Randomized Trials Network), we have performed a Genome-Wide Association Study (GWAS), using the Illumina Omni 1M SNP platform in 2,100 ischemic stroke patients from VISP. Extensive quality control (QC) measures were performed, resulting in a total of 737,081 SNPs for analysis. We have performed GWA analyses for baseline quantitative measures of creatinine, total cholesterol (TC), high density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), Factor 1+2 thrombin-antithrombin (TAT), tissue plasminogen activator (tPA), thrombomodulin (TM) and von Willebrand factor (vWF), using linear regression approaches implemented in PLINK. Principal component analysis (PCA), implemented in KING, was utilized to address confounders due to population substructure. Inverse normal transformation was performed for each of the quantitative traits, prior to analysis. Genome wide association analyses were performed using age, sex and the top 10 principal components as covariates. There is no inflation in our GWAS scan results (GC lambda ≤ 1.012 in all scans). We observed three associated loci that exceed genome wide significance (≤6.8×10 -8 ): in or near the CETP gene for HDL (6.5×10 -10 ), the CRP gene for CRP (7.4×10 -10 ), and at the ABO locus for vWF (8.7×10 -31 ). The most strongly associated SNPs for other traits were closest to the following genes: GABRA3 for creatinine ( rs994424 , 5.7×10 -6 ), SPATA13 for TC (rs9553189, 3.2×10 -7 ), between ARMCX2 and NXF5 genes on the X chromosome for TG (rs2213369, 1.7×10 -6 ); the ZIC4 gene for TAT (rs17565826, 4.1×10-6); LOC283089 for tPA (rs3011337, 3.6×10 -6 ); and JAZF1 for TM (rs10258132, 1.1×10 -6 ). Putative novel associations with these traits will require confirmation in larger independent samples. Our GWAS scan has successfully replicated associations for SNPs in the CETP, CRP and ABO genes for HDL, CRP and vWF respectively in an ischemic stroke population.
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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 | 0.001 | 0.001 |
| 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 | 0.000 |
| 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".