title: Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.
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.
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Ungvári
authors.forename: Gábor
authors.initials: G
authors.lastname: Hullám
authors.forename: Péter
authors.initials: P
authors.lastname: Antal
authors.forename: Petra Sz
authors.initials: PS
authors.lastname: Kiszel
authors.forename: András
authors.initials: A
authors.lastname: Gézsi
authors.forename: Éva
authors.initials: É
authors.lastname: Hadadi
authors.forename: Viktor
authors.initials: V
authors.lastname: Virág
authors.forename: Gergely
authors.initials: G
authors.lastname: Hajós
authors.forename: András
authors.initials: A
authors.lastname: Millinghoffer
authors.forename: Adrienne
authors.initials: A
authors.lastname: Nagy
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.forename: Ágnes F
authors.initials: ÁF
authors.lastname: Semsei
authors.forename: Gergely
authors.initials: G
authors.lastname: Temesi
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
authors.forename: Péter
authors.initials: P
authors.lastname: Kisfali
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
authors.forename: András
authors.initials: A
authors.lastname: Bikov
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gálffy
authors.forename: Lilla
authors.initials: L
authors.lastname: Tamási
authors.forename: András
authors.initials: A
authors.lastname: Falus
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000150:complications / Q000235:genetics*; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D030541:Databases, Genetic; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D055361:Multilevel Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012220:Rhinitis / Q000150:complications / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult