liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture
University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
Show others and affiliations
2015 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 97, no 6, 816-836 p.Article in journal (Refereed) PublishedText
Abstract [en]

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 x 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 x 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

Place, publisher, year, edition, pages
CELL PRESS , 2015. Vol. 97, no 6, 816-836 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-125163DOI: 10.1016/j.ajhg.2015.10.019ISI: 000368437900004PubMedID: 26626624OAI: diva2:903392

Funding Agencies|Barbara and Neal Henschel Charitable Foundation; NIH [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183, R01AR050266]; German Research Foundation; German Ministry of Education and Research (BMBF); Doris Duke Foundation [2013106]; Taubman Medical Research Institute; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); Ann Arbor Veterans Affairs Hospital

Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2016-02-15

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Enerbäck, Charlotta
By organisation
Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Dermatology and Venerology
In the same journal
American Journal of Human Genetics
Clinical Medicine

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: 175 hits
ReferencesLink to record
Permanent link

Direct link