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Objectives: The role was studied of multiple single nucleotide polymorphisms in tooth agenesis in the Hungarian population using a complex approach., Methods: Eight SNPs, PAX9 -912 C/T, PAX9 -1031 A/G, MSX1 3755 A/G, FGFR1 T/C rs881301, IRF6 T/C rs764093, AXIN2-8150 A/G, AXIN2-8434 A/G and AXIN2-30224 C/T, were studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers. Case-control analysis was performed to test both allelic and genotypic associations as well as associations at the level of haplotypes. Multivariate exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as well as logistic regression analysis were performed., Results: Conventional statistics showed that PAX9 SNP -912 C/T and the MSX1 SNP changed the incidence of hypodontia, although after Bonferroni correction for multiple hypothesis testing, the effects were only borderline tendencies. Using a statistical analysis better suited for handling multiple hypotheses, the BN-BMLA, PAX9 SNPs clearly showed a synergistic effect. This was confirmed by other multivariate analyses and it remained significant after corrections for multiple hypothesis testing (p < 0.0025). The PAX9-1031-A-PAX9-912-T haplotype was the most relevant combination causing hypodontia. Interaction was weaker between PAX9 and MSX1, while other SNPs had no joint effect on hypodontia., Conclusion: This complex analysis shows the important role of PAX9 and MSX1 SNPs and of their interactions in tooth agenesis, while IRF6, FGFR1 and AXIN2 SNPs had no detectable role in the Hungarian population. These results also reveal that risk factors in hypodontia need to be identified in various populations, since there is considerable variability among them.