uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis
Show others and affiliations
2011 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, no 2, 259-265 p.Article in journal (Refereed) Published
Abstract [en]

Background: Rheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets. Methods and results GWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case-control study EIRA. Imputation was performed which allowed comparisons using 1 723 056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 x 10(-8)) in the comparison between ACPA-negative RA and controls. A case-case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the RPS12P4 locus in chromosome 2 reached a p value of 2 x 10(6) and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA. Conclusions ACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease.

Place, publisher, year, edition, pages
2011. Vol. 70, no 2, 259-265 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-149064DOI: 10.1136/ard.2009.126821ISI: 000286179000005PubMedID: 21156761OAI: oai:DiVA.org:uu-149064DiVA: diva2:403771
Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2011-03-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Clinical Immunology
In the same journal
Annals of the Rheumatic Diseases
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
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

Altmetric score

Total: 145 hits
ReferencesLink to record
Permanent link

Direct link