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Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.

Ungvári I, Hullám G, Antal P, Kiszel PS, Gézsi A, Hadadi É, Virág V, Hajós G, Millinghoffer A, Nagy A, Kiss A, Semsei ÁF, Temesi G, Melegh B, Kisfali P, Széll M, Bikov A, Gálffy G, Tamási L, Falus A, Szalai C - PLoS ONE (2012)

Bottom Line: The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA).This method uses bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects.This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.

ABSTRACT
Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA). This method uses bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated.With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2-1.8); p = 3×10(-4)). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics.In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

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Related in: MedlinePlus

A possible dependency model in asthma.An example for a possible transitive association between IgE and Asthma. Although there is a possible direct relationship, IgE level may relate to asthma indirectly via eosinophil or a presence of allergy.
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pone-0033573-g003: A possible dependency model in asthma.An example for a possible transitive association between IgE and Asthma. Although there is a possible direct relationship, IgE level may relate to asthma indirectly via eosinophil or a presence of allergy.

Mentions: The association of a genetic variant to a phenotypic feature can have multiple types. First, because of the dependency of the genetic factors (due to linkage disequilibrium or evolutionary patterns), the markers typically found in genetic association studies are rarely directly associated to the phenotype. In these cases, the association is transitive, i.e. it is mediated by the causal SNP. For example, in case of PTGDR, the posterior of association of the SNPs (rs17831675, rs17831682, and rs803012) to asthma are larger than 0.9, but rs803012 can be excluded as strongly relevant, because its posterior of strong relevance is lower than 0.005, which indicates its non-causal, non-functional role. Second, in case of multiple targets, which originate potentially from a complex dependency model, the association can be mediated by phenotypic variables. For example in case of the asthma a possible dependency model is shown in Figure 3, in which a SNP affecting IgE might be both directly and transitively associated with asthma.


Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.

Ungvári I, Hullám G, Antal P, Kiszel PS, Gézsi A, Hadadi É, Virág V, Hajós G, Millinghoffer A, Nagy A, Kiss A, Semsei ÁF, Temesi G, Melegh B, Kisfali P, Széll M, Bikov A, Gálffy G, Tamási L, Falus A, Szalai C - PLoS ONE (2012)

A possible dependency model in asthma.An example for a possible transitive association between IgE and Asthma. Although there is a possible direct relationship, IgE level may relate to asthma indirectly via eosinophil or a presence of allergy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303848&req=5

pone-0033573-g003: A possible dependency model in asthma.An example for a possible transitive association between IgE and Asthma. Although there is a possible direct relationship, IgE level may relate to asthma indirectly via eosinophil or a presence of allergy.
Mentions: The association of a genetic variant to a phenotypic feature can have multiple types. First, because of the dependency of the genetic factors (due to linkage disequilibrium or evolutionary patterns), the markers typically found in genetic association studies are rarely directly associated to the phenotype. In these cases, the association is transitive, i.e. it is mediated by the causal SNP. For example, in case of PTGDR, the posterior of association of the SNPs (rs17831675, rs17831682, and rs803012) to asthma are larger than 0.9, but rs803012 can be excluded as strongly relevant, because its posterior of strong relevance is lower than 0.005, which indicates its non-causal, non-functional role. Second, in case of multiple targets, which originate potentially from a complex dependency model, the association can be mediated by phenotypic variables. For example in case of the asthma a possible dependency model is shown in Figure 3, in which a SNP affecting IgE might be both directly and transitively associated with asthma.

Bottom Line: The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA).This method uses bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects.This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.

ABSTRACT
Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA). This method uses bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated.With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2-1.8); p = 3×10(-4)). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics.In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance.

Show MeSH
Related in: MedlinePlus