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http://purl.uniprot.org/citations/29905830http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29905830http://www.w3.org/2000/01/rdf-schema#comment"

Background and aims

The genetic contribution to the prognosis of ulcerative colitis [UC] is poorly understood, and most currently known susceptibility loci are not associated with prognosis. To identify genetic variants influencing the prognosis of UC, we performed an Immunochip-based study using an extreme phenotype approach.

Methods

Based on the finding that the only association, Pdiscovery-meta <1 × 10-4, was located in the human leukocyte antigen [HLA], we focused our analyses on the HLA region. We performed the analysis using HLA imputation data from three independent discovery cohorts of 607 UC patients [243 poor-prognosis and 364 good-prognosis], followed by replication in 274 UC patients [145 poor-prognosis and 129 good-prognosis].

Results

We found that rs9268877, located between HLA-DRA and HLA-DRB, was associated with poor-prognosis of UC at genome-wide significance (odds ratio [ORdiscovery] = 1.82; ORreplication = 1.55; ORcombined-meta = 1.72, pcombined-meta = 1.04 × 10-8), with effect size [OR] increasing incrementally according to worsening of prognosis in each of the three independent discovery cohorts and the replication cohort. However, rs9268877 showed no association with UC susceptibility [ORcombined-meta = 1.07, pcombined-meta = 0.135]; rs9268877 influenced 30-year clinical outcomes, and the presence of the rs9268877 risk allele had a sensitivity of 80.0% and specificity of 38.1% for colectomy.

Conclusions

Our results provide new insights into prognosis-associated genetic variation in UC, which appears to be distinct from the genetic contribution to disease susceptibility. These findings could be useful in identifying poor-prognosis patients who might benefit from early aggressive therapy."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.org/dc/terms/identifier"doi:10.1093/ecco-jcc/jjy080"xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Han B."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Park S.H."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Yoon Y.S."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Lee H.S."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Song K."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Lee C.H."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Oh S.H."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Jung S."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Hong M."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Kim B.M."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Haritunians T."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Baek J."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Kim K.M."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Yang S.K."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"McGovern D.P.B."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Yu C.S."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Moon J.W."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/author"Ye B.D."xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/name"J Crohns Colitis"xsd:string
http://purl.uniprot.org/citations/29905830http://purl.uniprot.org/core/pages"1113-1121"xsd:string
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