title: A highly sensitive and specific genetic marker to diagnose aspirin-exacerbated respiratory disease using a genome-wide association study.
abstract: The aim of the present study was to develop a diagnostic set of single-nucleotide polymorphisms (SNPs) for discriminating aspirin-exacerbated respiratory disease (AERD) from aspirin-tolerant asthma (ATA) using the genome-wide association study (GWAS) data; the GWAS data were filtered according to p-values and odds ratios (ORs) using PLINK software, and the 10 candidate SNPs most closely associated with AERD were selected, based on 100 AERD and 100 ATA subjects. Using multiple logistic regression and receiver-operating characteristic (ROC) curve analysis, eight SNPs were chosen as the best model for distinguishing between AERD and ATA. The relative risk for AERD in each subject was calculated based on the relative risk of each of the eight SNPs. Ten of the original 109,365 SNPs highly associated (filtered with p<0.001 and ORs) with the risk for AERD were selected. A combination model of the eight SNPs among the 10 SNPs showed the highest area under the ROC curve of 0.9. The overall relative risk for AERD based on the eight SNPs was significantly different between the AERD and ATA groups (p=2.802E-21), and the sensitivity and specificity were 78% and 88%, respectively. The candidate set of eight SNPs may be useful in predicting the risk for AERD.
authors.affiliation: Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: JongSook
authors.initials: J
authors.lastname: Park
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Soo-taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Mi-kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: HyoungDoo
authors.initials: H
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D055963:Asthma, Aspirin-Induced / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012307:Risk Factors; D012984:Software; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin