Results of further association testing of candidate variants within individuals with severe RSV bronchiolitis in infancy, without including genotypes from the ESP.

<p>Phenotypes include physician diagnosed asthma, active asthma, persistent wheeze, and methacholine PC₂₀ at age 6 years. P-values < 0.05 are in bold italics, Freq = allele frequency, OR = odds ratio, SE = standard error.</p

Results of replication in the BRASS study of four variants associated with asthma following severe RSV bronchiolitis in infancy (number of asthma cases = 81, number of asthma controls = 126).

<p>Results of replication in the BRASS study of four variants associated with asthma following severe RSV bronchiolitis in infancy (number of asthma cases = 81, number of asthma controls = 126).</p

Summary of clinical characteristics of participants in the RBEL study.

<p>Abbreviations used: SaO₂ = lowest oxygen saturation recorded during index hospitalization; IgE = immunoglobulin E; FEV₁ = forced expiratory volume in one second; BD = bronchodilator; PC₂₀ = provocative concentration of methacholine that causes a 20% decline in FEV_1.</p><p>Summary of clinical characteristics of participants in the RBEL study.</p

Counts of rare and private rare variants in asthma cases vs. controls in anonymous pooled sequencing of coding exons of 131 candidate genes.

<p>Private variants are those private to either cases or controls within an ethnicity. NS = nonsynonymous, Syn = synonymous, NC = non-coding.</p

Iceberg plot showing how the majority of coding variants identified per gene are at minor allele frequencies (MAF) at or below 10% in both European American (EA, N = 39) and African American (AA, N = 49) asthma cases and controls following severe RSV bronchiolitis in infancy.

<p>A total of 131 asthma genes were sequenced; each vertical bar represents a gene with at least one coding variant detected in the sample.</p

Structural domains and crystal structure of ADRB2 (protein databank [PDR] structure 2r4r, images from LS-SNP/PDB [51]).

<p><b>(A)</b> Structural domains of ADRB2; rs1800888 is located in amino acid residue number 164 within a helical transmembrane domain (protein databank [PDB] structure 2r4r) (<b>B)</b> crystal structure of ADRB2 showing the location of rs1800888; solvent accessibility for the amino acid residue at rs1800888 is 41% (exposed). <b>(C)</b> Position conservation within protein superfamily (G-protein coupled receptor 1 family), red = high conservation, blue = low; 32% of protein sequences in the alignment contain the most frequent amino acid residue at rs1800888.</p

QQplot showing the results of association testing at nonsynonymous variants for physician-diagnosed asthma following severe RSV bronchiolitis in infancy.

<p>Genotypes from the exome sequencing project (ESP) were used as controls. The shaded area represents the 95% confidence interval.</p

Minor allele frequencies of four nonsynonymous variants associated with asthma following severe RSV bronchiolitis in the ASW, AFR, and EUR populations from the 1000 Genomes Project, and in European (EA) and African Americans (AA) from the Exome Sequencing Project (ESP).

<p>Minor allele frequencies of four nonsynonymous variants associated with asthma following severe RSV bronchiolitis in the ASW, AFR, and EUR populations from the 1000 Genomes Project, and in European (EA) and African Americans (AA) from the Exome Sequencing Project (ESP).</p

Overview of total and rare variants called in anonymous pooled sequencing of coding exons for 131 candidate genes using the SPLINTER algorithm.

<p>*MAF<5% in at least one pool.</p><p>EA = European American, AA = African American, MAF = minor allele frequency.</p