OS 05-01 PROX1 GENE CC GENOTYPE AS A MAJOR DETERMINANT OF EARLY ONSET OF T2D AND CARDIOVASCULAR COMPLICATIONS IN SLAVIC SUBJECTS FROM ADVANCE STUDY
Bibliographic record
Abstract
Objective: We have previously reported distinct genetic architectures of renal impairment in T2D patients of Slavic and Celtic origins participating in the ADVANCE trial (J Hypertens. 2015 Jun;33 Suppl 1:e3). Further analysis suggests that the major driver of the difference in the prevalence of T2D complications between Slavic and Celtic groups is due to an earlier onset of diabetes in Slavic patients. In an attempt to distinguish between environmental and genetic factors on age of onset of diabetes, we have determined the age of onset of T2D in Slavic subjects living in Celtic countries and confirmed the same earlier onset (-2 years) in these subjects, notwithstanding their living environment. Design and Method: We performed GWAS analyses of age of onset of T2D in 3500 T2D patients from ADVANCE trial. Analyses were done for Celtic and Slavic groups separately and combined. Results: 7 loci are associated to age of onset of T2D in patients of both Celtic and Slavic origins, including HDAC9 gene (rs1128745). 9 loci are selectively associated to this phenotype in patients of Celtic origin, including the Il23R (rs1273974) while 9 different loci are associated to it in Slavic patients only. Among the latter, PROX1/PROX1-AS1 genes (rs340841) has the highest effect size. SNP rs 340841 homozygous CC genotype is associated with 2 years earlier onset of T2D in Slavic patients living in Slavic countries or in Celtic countries. This locus is also associated with eGFR decline in Slavic, with macroalbuminuria and hypertension in all ADVANCE subjects of Caucasian origin and with Interleukin-6 levels at baseline. In recent literature search we found that PROX1 gene has been associated with abnormalities of glucose metabolism and risk of diabetes with variations depending on ethnicity. Conclusions: We conclude that fine granularity of distinction in geo-ethic background assist in resolution of clinically relevant genetic contribution to cardiovascular complication in T2D.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".