Association of farm life with gene expression of TLR signaling cascade.

<p>Boldface values are significant (p<0.05).</p><p>*adjusted for sex, age, mother atopic sensitization and father atopic sensitization.</p><p>GMR, geometric mean in farmers’ children compared with non-farmers’ children.</p

Association of PRR and molecules of the TLR signaling cascade with CSR to IgE.

<p>Boldface values are significant (p<0.05).</p><p>*adjusted for sex, age, mother atopic sensitization and father atopic sensitization.</p><p>OR, odds ratio of farmers’ children compared with non-farmers’ children.</p

Association of farm life with the expression of cytokine genes.

<p>Boldface values are significant (p<0.05).</p><p>*adjusted for sex, age, mother atopic sensitization and father atopic sensitization.</p><p>GMR, geometric mean in farmers’ children compared with non farmers’ children.</p>1<p>Binomial values.</p

Characteristics of the children.

<p>*Chi-square test farmer vs non-farmer.</p><p>Mother or father atopic sensitization was defined as ever having asthma or rhinoconjunctivitis.</p><p>Children with reported doctor-diagnosed asthma once or obstructive bronchitis more than once in their lifetime were defined as having asthma ever.</p><p>Rhinoconjunctivitis was defined by reported doctor diagnosis of allergic rhinitis ever.</p><p>Atopic sensitization was assessed for 314 of the 316 children.</p

Association of farm life with gene expression of markers of T helper cell subtypes.

<p>Boldface values are significant (p<0.05).</p><p>*adjusted for sex, age, mother atopic sensitization and father atopic sensitization.</p><p>GMR, geometric mean in farmers’ children compared with non farmers’ children.</p

Visualization of co-occurring factors in rules for allergic eczema, asthma and atopic sensitization in PARSIFAL.

<p>Rule networks for (<b>A</b>-<b>B</b>) allergic eczema, (<b>C</b>-<b>D</b>) asthma and (<b>E</b>-<b>F</b>) atopic sensitization; affected and unaffected, respectively. Conditions that occur in the rules are on the outer ring, and co-occurrences of conditions in the rules are illustrated by ribbons across the circle connecting the conditions. The ribbon color indicates high (red) to low (grey) scores. The width of the edges is proportional to the number of correctly classified children.</p

SNP combinations with relevance for current asthma and wheeze in BAMSE and PARSIFAL.

<div><p>The combination of specific genetic variants in (<b>A</b>) <i>ORMDL3-RORA</i> increases the risk for current asthma¹, and in (<b>B</b>) <i>ORMDL3-RORA-COL29A1</i> increase the risk for wheeze². The risk for current asthma and wheeze increased with the number of risk genotypes described by corresponding rule (<b>C</b>-<b>D</b>). ORs and 95% confidence interval are shown. The major allele count is indicated for each gene below i.e. describing 0, 1 or 2 copies of the major allele. The reference category includes children who do not fulfill the rule.</p> <p>¹ IF ORMDL3_rs2305480=2[GG] AND RORA_rs17270362=1[AG] THEN current asthma.</p> <p>² IF COL29A1_rs11917356=2[AA] AND ORMDL3_rs7216389=0[TT] AND RORA_rs17270362=1[AG] THEN wheeze.</p></div

Combinations of genetic variants and/or environmental factors in relation to allergy and asthma in PARSIFAL.

<p>Odds ratios are shown for the top-hits rules identified for (<b>A</b>) allergic eczema; affected^1-10 and unaffected^58-67 (<b>B</b>) asthma; affected^1-10 and unaffected^44-53 and (<b>C</b>) atopic sensitization; affected^1-10 and unaffected^37-46. The odds ratios were calculated for children that fulfill all conditions in the rule using all other children as reference.</p

Analysis methodology for factors related to childhood allergy in the epidemiologic studies BAMSE and PARSIFAL.

<p>Allergy phenotypes were modeled based on genetic and exposure data to identify (<b>A</b>) rules using gene and (<b>B</b>) gene and environment data. MCFS selected significant predictors of a phenotype, which was used to generate rules by ROSETTA. First model used 110 SNPs in BAMSE and PARSIFAL, while the second model included both genetic and exposure data in PARSIFAL, using BAMSE for validation when applicable.</p

Overview of the genomic location and correlations of the <i>RORA</i> SNPs analyzed in this study.

<p>(<b>A</b>) Schematic representation of the exon intron distribution of the longest isoform of <i>RORA</i> (NM_134231) located in chromosome 15q22.2 and the position of the GWAS SNP rs11071559. An expansion of the 116.5 kb region surrounding the rs11071559 reveals the 35 SNPs analyzed in this study according to their positions along the intron 1. (<b>B</b>) The LD structure of the 116.5 kb region of RORA as defined by the solid spine algorithm in the combined dataset (n = 3153). Numbers in each box correspond to the pair-wise linkage disequilibrium coefficients (D’) between the respective SNPs. A similar LD structure was observed in BAMSE and PARSIFAL as separated populations. Additional information on the 35 <i>RORA</i> SNPs is presented in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060111#pone.0060111.s003" target="_blank">Table S3</a></b>.</p