Fine mapping and comprehensive resequencing analysis of a region of chromosome 11q13 reveals multiple independent loci associated with prostate cancer
Bibliographic record
Abstract
Two genome-wide association studies of prostate cancer identified single nucleotide polymorphism (SNP) markers in a region of chromosome 11q13. As part of the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative the region flanking the most significant marker, rs10896449, was fine mapped using common single nucleotide polymorphisms (SNPs) selected from a two-staged tagging strategy. Of the 120 SNPs analyzed in 10,272 cases and 9,123 controls of European origin, single locus analysis identified 18 SNPs below genome-wide significance (P < 10−8); rs10896449, initially reported remained most significant (P = 7.94 × 10−19). Multi-locus models that included the 18 significant SNPs sequentially identified a second association at rs12793759 (OR = 1.14 P = 4.76 × 10−5), independent of rs10896449 that remained significant after adjustment for multiple testing within the region. A third signal, rs10896438 (OR = 1.07, P = 5.92 × 10−3), independent of both rs10896449 and rs12793759 was detected. To comprehensively catalog genetic variants in strong LD with the above SNPs as well as to determine the region's LD pattern, next-generation sequence analysis of 123 kb (chr11: 68,642,755 - 68,765,690) was performed in 75 individuals of European origin. 447 SNPs with minor allele frequency (MAF) > 1% were identified, which included 180 novel SNPs. Based on r2 > 0.8, 105 SNPs are needed to monitor SNPs with MAF > 1%, whereas 62 SNPs are required for MAF > 5%. 51 SNPs with MAF > 5% are not monitored with r2 > 0.8; 24 singletons (most of which were monitored with r2 > 0.6) and 27 SNPs in 9 correlation bins (r2 > 0.8). For the strongest hits, rs10896449, rs12793759 and rs10896438, 26, 6 and 18 SNPs are correlated with r2 > 0.8, respectively. Our results illustrate the complex architecture of the common genetic variants conferring prostate cancer risk on chromosome 11q13. The fine mapping and sequence analysis point towards a subset of SNPs worthy of follow-up studies designed to understand the molecular basis of the susceptibility alleles.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 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".