Roles of Genetic Polymorphisms in the Folate Pathway in Childhood Acute Lymphoblastic Leukemia Evaluated by Bayesian Relevance and Effect Size Analysis

... minor allele frequencies (MAF) for the investigated polymorphisms are reported in Table S3 . The frequentist statistical analysis revealed that 9 SNPs (rs2235013, rs12517451, rs1544105, rs1076991, rs12759827, rs9909104, rs2853533, rs3776455, rs1532268) in 8 genes ( ABCB1, DHFR, FPGS, MTHFD1, MTR, SHMT1, TYMS, MTRR ) reached the p<0.05 values ( Table S4 ), but due to the multiple testing, statistical corrections were applied. In this way 2 SNPs of the MTHFD1 and MTRR genes reached the FDR=5% (p1.21E

... ( MTHFD1 rs1076991, MTRR rs3776455) and found that the rs3776455 SNP in MTRR gene, was in strong linkage with other six SNPs (rs2966952, rs1801394, rs326120, rs1532268, rs162036, and rs10380) in the gene. It suggests that the rs3776455 SNP can determine the status of the other six SNPs, and thus can be regarded as a tagSNP. Effect of the investigated SNPs on the survival rates of the Hungarian ALL population Earlier we have already reported the survival rate of this population in more details [41] . In

... most relevant variables in different sample groups according to the BN-BMLA. Variables ALL susceptibility B-ALL susceptibility T-ALL susceptibility HD-ALL susceptibility Gender 0.01 0.05 0.71 0.05 rs1076991 MTHFD1 0.65 0.53 0.13 0.00 rs1004474 TYMS 0.00 0.00 0.26 0.66 rs1532268 MTRR 0.00 0.03 0.21 0.68 rs3776455 MTRR 0.35 0.08 0.02 0.76 rs1222809 DHFR 0.00 0.01 0.12 0.43 rs11545078 GGH 0.03 0.06 0.16 0.33 rs3780127 GGH 0.03 0.06 0.16 0.33 In the hyperdiploid sample group, the relevant SNPs were rs3776455 and rs1532268 in the MTRR gene (probability of strong relevance to HD-ALL was 0.76 and 0.68, respectively), and rs1004474 in TYMS (0.66). The SNP rs3776455 in the MTRR gene was selected as the best univariate model by MDR with an overall accuracy score of 0.5724. MDR found the other two SNPs relevant only in interaction as described later. A few other SNPs also showed low probabilities of relevance in ALL susceptibility (see Figure 2 ). 10.1371/journal.pone.0069843.g002 Figure 2 Illustration

... all measured SNPs (rs2966952, rs1801394, rs326120, rs1532268, rs162036, rs3776455 and rs10380) had around 0.65 probability of being associated to ALL, but only rs3776455 had a moderately high probability of strong relevance, meaning that the associations were mainly affected through this SNP. In the B-cell lineage sample group, three SNPs (rs1076991, rs2236225 and rs745686) in MTHFD1 gene showed association to ALL with probabilities between 0.570.67, mediated by rs1076991. Both in the overall ALL

..., rs162036 and rs10380) were associated (0.790.82) via rs1532268 and rs3776455 ( Table S8 ). Structural interactions, statistical interactions and redundancies We examined different types of interactions, namely structural interactions, statistical interactions and redundancies between the strongly relevant variables. In cases of the overall, B- and T-cell lineage sample groups, the analyses revealed no pure interactional effect (see explanations in Table S7 ), i.e. the probability of pure interaction

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