Bayesian, Systems-based, Multilevel Analysis of Associations for Complex Phenotypes: from Interpretation to Decision

Antal, Péter; Millinghoffer, András; Hullám, Gábor; Hajós, Gergely; Sarkozy, Peter; Gézsi, András; Szalai, Csaba; Falus, András

doi:10.1093/acprof:oso/9780198709022.003.0013

Cited by 9 publications

(10 citation statements)

References 35 publications

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“…Additionally, it can be difficult to differentiate AR from other common diseases, such as non-allergic rhinitis (NAR) and chronic rhinosinusitis, as these diseases share similar symptoms with AR in young children. These similarities are particularly common in preschool-aged children 18. We diagnosed current AR as nasal symptoms and also used physician diagnoses to reduce potential errors in the misdiagnosis of AR.…”

Section: Discussionmentioning

confidence: 99%

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

Yoon

Choi

Lee

et al. 2017

Allergy Asthma Immunol Res

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PurposeThe nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO).MethodsThis general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR.ResultsThe prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083).ConclusionsMold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.

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Section: Discussionmentioning

confidence: 99%

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

Yoon

Choi

Lee

et al. 2017

Allergy Asthma Immunol Res

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“…Bayesian networks offer a rich language for genetic association studies, because they exhaustively and exactly represent strongly relevant variables and their interactions through the Markov Blanket Set and Markov Blanket Graph features and they are able to evaluate multiple targets. Furthermore, this Bayesian global relevance analysis method provides posterior probabilities, which are direct statements about hypotheses; thus, it can also be used to construct probabilistic data analytic knowledge bases in genetic association studies to support complex querying, off-line meta-analysis, and fusion with background knowledge 18192021…”

Section: Methodsmentioning

confidence: 99%

“…, SNP), on the other hand 0 means that there is no such relationship. Posterior probabilities of strong relevance greater than or equal to 0.5 are regarded as relevant, and above 0.75 as convincing 18192021…”

Section: Methodsmentioning

confidence: 99%

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

Fodor

Gézsi

Ungvári

et al. 2017

Allergy Asthma Immunol Res

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PurposeSeveral lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes.MethodsThe levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA).ResultsThe mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other.ConclusionsOur results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.

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“…A relevant relationship was defined when the probability was >0.3. The applied method was developed by our research team; for further details see the section in the book “Probabilistic graphical models for genetics” [34]. …”

Section: Methodsmentioning

confidence: 99%

Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma

et al. 2016

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Inter-individual differences in toxic symptoms and pharmacokinetics of highdose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato-and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1, ABCC2, ABCC3, ABCC10, ABCG2, GGH, SLC19A1 and NR1I2 genes were analyzed in 59 patients with osteosarcoma. Univariate association analysis and Bayesian network-based Bayesian univariate and multilevel analysis of relevance (BN-BMLA) were applied. Rare alleles of 10 SNPs of ABCB1, ABCC2, ABCC3, ABCG2 and NR1I2 genes showed a correlation with the pharmacokinetic values and univariate association analysis. The risk of toxicity was associated with five SNPs in the ABCC2 and NR1I2 genes. Pharmacokinetic parameters were associated with four SNPs of the ABCB1, ABCC3, NR1I2, and GGH genes, and toxicity was shown to be associated with ABCC1 rs246219 and ABCC2 rs717620 using the univariate and BN-BMLA method. BN-BMLA analysis detected relevant effects on the AUC 0-48 in the following SNPs: ABCB1 rs928256, ABCC3 rs4793665, and GGH rs3758149. In both univariate and multivariate analyses the SNPs ABCB1 rs928256, ABCC3 rs4793665, GGH rs3758149, and NR1I2 rs3814058 SNPs were relevant. These SNPs should be considered in future dose individualization during treatment.

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Bayesian, Systems-based, Multilevel Analysis of Associations for Complex Phenotypes: from Interpretation to Decision

Cited by 9 publications

References 35 publications

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma

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