Gene Map and LD Plot of <i>VEGF</i> Gene

<p>Color scheme is based on D′ and logarithm of the odds of linkage (LOD) score values: white D′ < 1 and LOD < 2, blue D′ = 1 and LOD < 2, shades of pink/red: D′ < 1 and LOD ≥ 2, and bright red D′ = 1 and LOD ≥ 2. Numbers in squares are D′ values (values of 1.0 are not shown). Block definition is based on the Gabriel et al. method [34]. Two (rs3024989 and rs367173) of the 29 SNPs determined are not shown because of low variation in this population. Red rectangles in the gene map represent exons.</p

Phylogenetic Trees for <i>VEGF</i> Haplotypes and Association with Bladder Cancer Risk among 926 Cases and 900 Controls with DNA in the iPLEX Assay, Spanish Bladder Cancer Study

<div><p>See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030029#pgen-0030029-g001" target="_blank">Figure 1</a> for block definitions. Of the 29 <i>VEGF</i> SNPs determined, two had low genotypic variation in our population; therefore, haplotype analyses were based on the remaining 27 SNPs. Polymorphic bases are in 5′ to 3′ order: Block 1(<b>rs833052</b> and rs866236); Block 2 (<b>rs1109324</b>, <b>rs1547651</b>, rs833060, rs699947, rs1005230, rs833061, rs1570360, rs2010963, <b>rs25648</b>, rs833067, rs3025042, rs833068, <b>rs3024994</b>, rs735286, rs3024998, rs3025000, and rs3025006); and Block 3 (rs3025030, rs3025033, rs3025035, and rs3025036). Bolded rs numbers are for individual SNPs significantly associated with bladder cancer risk.</p><p>Eleven cases and 13 controls with missing data on more than 15 of the 17 SNPs in Block 2 were excluded from haplotype analyses because their inclusion resulted in lack of convergence. Nucleotide changes significantly associated with risk in the individual genotype analyses are shown in boxes. The most common haplotye is the reference category. Haplotypes with the common variant for each individual SNP are CC for Block 1, GAGCCGTGCTGGCCCCC for Block 2, and GACC for Block 3.</p></div

Risk estimates from Bayesian Threshold LASSO model (BTL), considering a posterior probability of 75%, and from logistic regression analyses among non-smokers.

a<p>Posterior mean of the OR, calculated from the BTL analyses. Similar values for the median were obtained for each SNP.</p>b<p>It corresponds to , where .</p>c<p>OR obtained from the adjusted logistic regression.</p>d<p><i>p</i>-value of the trend obtained from the adjusted logistic regression.</p><p>SNPs also selected by AUC-RF are bold-faced.</p

Risk estimates of Bayesian Threshold LASSO model (BTL), considering a posterior probability higher than 80%, and from logistic regression for the total population.

<p>^a Posterior mean of the OR, calculated from the BTL analyses Similar values for the median were obtained for each SNP.</p><p>^b It corresponds to , where .</p><p>^c OR obtained from the adjusted logistic regression.</p><p>^d<i>p</i>-value of the trend obtained from the adjusted logistic regression.</p><p>SNPs also selected by AUC-RF are bold-faced.</p

Histogram of the posterior probabilities of having a positive (negative) SNP effect by Bayesian Threshold LASSO model (BTL) in the total population.

<p>The dot point line indicates the cut-off point of 80% above which SNPs were considered.</p

Venn diagrams showing the overlapping between the SNPs selected by Bayesian Threshold model (BTL) and AUC-Random Forest (AUC-RF).

<p>(A) Number of SNPs detected by each method in the total population. (B) Number of SNPs detected by each method in the non-smoker subset. (C) Number of common SNPs detected by BTL in the total population and non-smoker subset, with posterior probabilities of at least 80% and 75% of having an effect different from 0. (D) Number of SNPs detected by AUC-RF in both the total population and the non-smoker subset.</p

Relative variable importance for the top 12 polymorphisms selected by AUC-RF in the total population.

a<p>Calculated by dividing the raw variable importance measurement by that with the highest MDG, that of smoking status.</p

Main effect <i>p-values</i> for bladder cancer risk (overall and for each subphenotype) for each tag-SNP under the additive mode of inheritance.

<p>A SNP <i>p-value</i> above the red line is considered as associated with the phenotype after multiple testing correction by Bonferroni (4.2 for main effects and 3.6 for subtypes). All models are adjusted for age, gender, region and cigarette smoking status.</p

SNPs in <i>TP53</i> and bladder cancer risk.

<p><i>Repr. (%)</i>,percentage reproducibility assessing the robustness of each SNP by LASSO.</p><p>AA, Aa and aa represent common-homozygotes, heterozygotes and rare-allele homozygotes, respectively.</p><p>OR, odds ratio; CI, confidence interval; OR(Aa) and OR(aa) were estimated relative to genotype AA.</p>1<p>Arg72Pro polymorphism.</p><p>All models were adjusted for age, gender, region and cigarette smoking status.</p

Demographics and smoking status of patients included in the study.

1<p><i>p-value</i> from Pearson's χ² test for association.</p