title: Genome-wide association study of serious blistering skin rash caused by drugs.
abstract: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe, potentially life threatening adverse drug reactions characterized by skin blistering. Previous studies have identified drug-specific and population-specific genetic risk factors with large effects. In this study, we report the first genome-wide association study (GWAS) of SJS/TEN induced by a variety of drugs. Our aim was to identify common genetic risk factors with large effects on SJS/TEN risk. We conducted a genome-wide analysis of 96 retrospective cases and 198 controls with a panel of over one million single-nucleotide polymorphisms (SNPs). We further improved power with about 4000 additional controls from publicly available datasets. No genome-wide significant associations with SNPs or copy number variants were observed, although several genomic regions were suggested that may have a role in predisposing to drug-induced SJS/TEN. Our GWAS did not find common, highly penetrant genetic risk factors responsible for SJS/TEN events in the cases selected.
authors.affiliation: Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10027, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: P
authors.initials: P
authors.lastname: Nicoletti
authors.forename: A
authors.initials: A
authors.lastname: Floratos
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: M
authors.initials: M
authors.lastname: Molokhia
authors.forename: P
authors.initials: P
authors.lastname: Geppetti
authors.forename: S
authors.initials: S
authors.lastname: Benemei
authors.forename: B
authors.initials: B
authors.lastname: Giomi
authors.forename: D
authors.initials: D
authors.lastname: Schena
authors.forename: A
authors.initials: A
authors.lastname: Vultaggio
authors.forename: R
authors.initials: R
authors.lastname: Stern
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.forename: S
authors.initials: S
authors.lastname: John
authors.forename: M R
authors.initials: MR
authors.lastname: Nelson
authors.forename: I
authors.initials: I
authors.lastname: Pe'er
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D025341:Principal Component Analysis; D012189:Retrospective Studies; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000209:etiology* / Q000235:genetics