PT  - JOURNAL ARTICLE
AU  - MA Rivas
AU  - D Graham
AU  - P Sulem
AU  - C Stevens
AU  - AN Desch
AU  - P Goyette
AU  - D Gudbjartsson
AU  - I Jonsdottir
AU  - U Thorsteinsdottir
AU  - F Degenhardt
AU  - S Mucha
AU  - MI Kurki
AU  - D Li
AU  - M D’Amato
AU  - V Annese
AU  - S Vermeire
AU  - R Weersma
AU  - J Halfvarson
AU  - P Paavola-Sakki
AU  - M Lappalainen
AU  - M Lek
AU  - B Cummings
AU  - T Tukianen
AU  - T Haritunians
AU  - L Halme
AU  - LLE Koskinen
AU  - A Ananthakrishnan
AU  - Y Luo
AU  - GA Heap
AU  - M Visschedijk
AU  - NIDDK IBD Genetics Consortium
AU  - UK IBD Genetics Consortium
AU  - DG MacArthur
AU  - BM Neale
AU  - T Ahmad
AU  - CA Anderson
AU  - SR Brant
AU  - R Duerr
AU  - M Silverberg
AU  - J Cho
AU  - A Palotie
AU  - P Saavalainen
AU  - K Kontula
AU  - M Färkkilä
AU  - DPB McGovern
AU  - A Franke
AU  - K Stefansson
AU  - JD Rioux
AU  - RJ Xavier
AU  - MJ Daly
TI  - A protein truncating R179X variant in <em>RNF186</em> confers protection against ulcerative colitis
AID  - 10.1101/035105
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 035105
4099  - http://biorxiv.org/content/early/2015/12/23/035105.short
4100  - http://biorxiv.org/content/early/2015/12/23/035105.full
AB  - We conducted a search for protein truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. We found that a protein truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P = 6.89×10−7, odds ratio (OR) = 0.30). We further demonstrate that the truncated protein is expressed, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization or loss of an essential protein element.