RT Journal Article
SR Electronic
T1 A protein truncating R179X variant in <em>RNF186</em> confers protection against ulcerative colitis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 035105
DO 10.1101/035105
A1 MA Rivas
A1 D Graham
A1 P Sulem
A1 C Stevens
A1 AN Desch
A1 P Goyette
A1 D Gudbjartsson
A1 I Jonsdottir
A1 U Thorsteinsdottir
A1 F Degenhardt
A1 S Mucha
A1 MI Kurki
A1 D Li
A1 M D’Amato
A1 V Annese
A1 S Vermeire
A1 R Weersma
A1 J Halfvarson
A1 P Paavola-Sakki
A1 M Lappalainen
A1 M Lek
A1 B Cummings
A1 T Tukianen
A1 T Haritunians
A1 L Halme
A1 LLE Koskinen
A1 A Ananthakrishnan
A1 Y Luo
A1 GA Heap
A1 M Visschedijk
A1 NIDDK IBD Genetics Consortium
A1 UK IBD Genetics Consortium
A1 DG MacArthur
A1 BM Neale
A1 T Ahmad
A1 CA Anderson
A1 SR Brant
A1 R Duerr
A1 M Silverberg
A1 J Cho
A1 A Palotie
A1 P Saavalainen
A1 K Kontula
A1 M Färkkilä
A1 DPB McGovern
A1 A Franke
A1 K Stefansson
A1 JD Rioux
A1 RJ Xavier
A1 MJ Daly
YR 2015
UL http://biorxiv.org/content/early/2015/12/23/035105.abstract
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.