Re-Sequencing of the <b><i>APOL1</i></b>-<b><i>APOL4</i></b> and <b><i>MYH9</i></b> Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression
Bibliographic record
Abstract
<b><i>Background:</i></b> In African Americans (AAs), <i>APOL1</i> G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the <i>APOL1</i> loci, since earlier age ESKD is observed in some AAs with one <i>APOL1</i> renal-risk variant, and because the adjacent gene <i>MYH9</i> is associated with nephropathy in populations lacking G1 and G2 variants. <b><i>Methods:</i></b> Re-sequencing was performed across a ∼275 kb region encompassing the <i>APOL1-APOL4</i> and <i>MYH9</i> genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single <i>APOL1</i> G1 or G2 risk variant. <b><i>Results:</i></b> Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare <i>APOL3</i> Gln<sup>58</sup>Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for <i>APOL1</i> G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with <2 <i>APOL1</i> G1 and/or G2 alleles (849 cases; 1,139 controls), the <i>APOL3</i> null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. <b><i>Conclusion:</i></b> Additional common variants in the <i>APOL1-APOL4</i>-<i>MYH9</i> region do not contribute significantly to ESKD risk beyond the <i>APOL1</i> G1 and G2 alleles.
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 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 | 0.008 | 0.007 |
| Meta-epidemiology (narrow) | 0.006 | 0.005 |
| Meta-epidemiology (broad) | 0.011 | 0.005 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.004 | 0.014 |
| Scholarly communication | 0.001 | 0.003 |
| Open science | 0.006 | 0.003 |
| Research integrity | 0.003 | 0.005 |
| 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; both teacher heads agree on what is shown here.
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".