oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
deCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Show others and affiliations
2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 12342Article in journal (Refereed) Published
Abstract [en]

Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted 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=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.

Place, publisher, year, edition, pages
London, United Kingdom: Nature Publishing Group, 2016. Vol. 7, 12342
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-51667DOI: 10.1038/ncomms12342ISI: 000380952600001PubMedID: 27503255Scopus ID: 2-s2.0-84981165781OAI: oai:DiVA.org:oru-51667DiVA: diva2:955171
Note

Funding Agencies:

National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) DK064869  DK062432

National Human Genome Research Institute (NHGRI) DK064869  DK043351  HG005923

Crohns and Colitis Foundation 3765

Leona M. & Harry B. Helmsley Charitable Trust 2015PG-IBD001

Amgen 2013583217

CCFA 3765

Cedars-Sinai F. Widjaja Foundation

European Union DK062413  AI067068  U54DE023789-01  305479

Leona M. and Harry B. Helmsley Charitable Trust

Crohn's and Colitis Foundation of America

NIH DK062431  U01 DK062429  U01 DK062422  R01 DK092235  U01 DK062420

Medical Research Council, UK MR/J00314X/1

Wellcome Trust WT091310  098051

Inflammatory Bowel Disease Genetic Research Chair at the University of Pittsburgh PO1DK046763

Available from: 2016-08-24 Created: 2016-08-16 Last updated: 2016-09-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Halfvarson, Jonas
By organisation
School of Medical Sciences
In the same journal
Nature Communications
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 122 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf