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

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

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

Baseline clinical characteristics.

<p>Baseline clinical characteristics.</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

Study design, participant and procedure flow.

<p>Reasons for screen failures were: Elevated alanine aminotransferase level (N = 5); % predicted forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) < 90% (N = 6); minimal airway obstruction on pulmonary function testing (N = 1); abnormal chest x-ray (N = 1); abnormal electrocardiogram (N = 1); history of childhood asthma (N = 1); smoking within 1 year of enrollment (N = 1); body mass index outside range (N = 1). Withdrawals were volunteers who signed the consent after completing the screening procedures and were given the blinded study drugs but withdrew from the study prior to initiating the imaging and bronchoscopy procedures and were lost to follow up. FDG-PET = positron emission tomography imaging with ¹⁸F-fluorodeoxyglucose. i.b. = intrabronchial. qD = once per day. Q6hr = once every six hours.</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