Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7046
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Funding
- Arthritis Research UK [20385]
- NIHR Manchester Musculoskeletal Biomedical Research Unit
- National Institute for Health Research Biomedical Research Unit Funding Scheme
- Science Foundation Ireland [SFI09/IN.1/B2640]
- German Federal Ministry of Education and Research ArthroMark [01 EC 1009C]
- Federal State of Hesse (LOEWE-project: IME Fraunhofer Project Group Translational Medicine & Pharmacology at the Goethe University)
- Pfizer Pharma, Germany
- Abbvie Plc
- National Health and Medical Research Foundation (Australia) Senior Principal Research Fellowship
- Wellcome Trust [089989, 091157]
- JDRF [9-2011-253]
- Wellcome Trust Strategic Award [100140]
- MRC [G1000417, MR/L01629X/1] Funding Source: UKRI
- Medical Research Council [G1000417, MR/L01629X/1, 1233349] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10105] Funding Source: researchfish
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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 the IL23R locus. 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.
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