André Reis and colleagues report a genome-wide association study identifying a susceptibility locus at TRAF3IP2 for psoriatic arthritis and psoriasis. Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10−17). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10−3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10−20, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case–control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at theIL23Rlocus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8⁺memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

The study included 150 individuals with AMI who were referred to the Centre of Atherosclerosis at the Medical School of the Tor Vergata University of Rome. All cases were clinically evaluated and all underwent coronary angiography and left ventriculography. The diagnosis of AMI was based on typical electrocardiographic changes and increased serum activities of at least two enzymes, such as creatine kinase, aspartate aminotransferase, and lactate dehydrogenase. The diagnosis was confirmed by the presence of wall motion abnormality on left ventriculography and attendant stenosis (>50%) in any of the major coronary arteries or in the left main coronary artery on coronary angiography. One hundred and three control subjects were recruited from persons found to have at least one conventional risk factor for coronary artery disease (CAD), such as cigarette smoking (10 cigarettes daily), hypertension (systolic blood pressure of 140 mm Hg or diastolic blood pressure 90 mm Hg), diabetes mellitus (blood glucose level 126 mg per decilitre (6.93 mmol per litre)), hypercholesterolaemia (total serum cholesterol level 220 mg per decilitre (5.72 mmol per litre)). These subjects had no evidence of active myocardial ischaemia, but underwent left ventriculography and coronary angiography as part of valvular disease. All these control subjects were found to have normal coronary arteries. The mean age of the AMI patients was 64.4 (5.8 years) (mean (SD)) with a mean age at onset of symptoms 60.4 (4.5) years. The mean age of the control subjects was 63.4 (6.2) years. The study was approved by the Tor Vergata University Ethics Committee.