Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
Publication Title
Nature genetics
Document Type
Article
Publication Date
2-1-2017
Keywords
Adaptor Proteins, Signal Transducing; Alleles; Cholangitis, Sclerosing; Colitis, Ulcerative; Genome-Wide Association Study; Humans; Inflammatory Bowel Diseases; Polymorphism, Single Nucleotide; RNA, Messenger; Risk Factors
Abstract
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (r
Area of Special Interest
Digestive Health
Specialty/Research Institute
Gastroenterology
