uu.seUppsala University Publications
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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
Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Jeffrey Cheah Biomed Ctr, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge CB2 0AW, England.
Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Univ Cambridge, Dept Publ Hlth & Primary Care, BHF Cardiovasc Epidemiol Unit, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England;Hlth Data Res UK, Cambridge, England.
Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;San Carlo Borromeo Hosp, Nephrol & Immunopathol Unit, ASST Santi Paolo & Carlo, Milan, Italy;Univ Milan, Dipartimento Sci Salute, Milan, Italy.ORCID iD: 0000-0002-1686-5709
Univ Cambridge, Sch Clin Med, Dept Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Cambridge Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge Biomed Campus,Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
Show others and affiliations
2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 5120Article in journal (Refereed) Published
Abstract [en]

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 5120
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-398078DOI: 10.1038/s41467-019-12515-9ISI: 000495858500001PubMedID: 31719529OAI: oai:DiVA.org:uu-398078DiVA, id: diva2:1374691
Available from: 2019-12-02 Created: 2019-12-02 Last updated: 2019-12-02Bibliographically approved

Open Access in DiVA

fulltext(1518 kB)4 downloads
File information
File name FULLTEXT01.pdfFile size 1518 kBChecksum SHA-512
85676bd4d71f243fa38656986fc6c3a98fa0f2fb55a5cc5dd1b24dba08dccdc5cacf4c83d9415e313be962f95f7dc621e224d145a15a94625daa88f11b2b0808
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Knight, Ann

Search in DiVA

By author/editor
Alberici, FedericoLittle, Mark A.Knight, Ann
By organisation
Rheumatology
In the same journal
Nature Communications
Rheumatology and Autoimmunity

Search outside of DiVA

GoogleGoogle Scholar
Total: 4 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 22 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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