Type

Journal Article

Authors

Ross Mcmanus
Gary Donohoe

Subjects

Medicine & Nursing

Topics
genetic loci inflammatory arthritis national institute education research case control study health research biomedical research psoriatic arthritis psa

Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis (2015)

Abstract Poriatic 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 þ memory primary Tcells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA. We acknowledge the assistance given by IT Services and the use of the Computational Shared Facility (CSF) at The University of Manchester. We thank Arthritis Research UK for their support (grant number 20385) and the NIHR Manchester Musculoskeletal Biomedical Research Unit. This report includes independent research funded by the National Institute for Health Research Biomedical Research Unit Funding Scheme. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Genotyping of Irish samples was partially funded by Science Foundation Ireland grant number SFI09/IN.1/B2640. Support for the German component of the study was received from the German Federal Ministry of Education and Research ArthroMark (project 4, 01 EC 1009C), the Federal State of Hesse (LOEWE-project: IME Fraunhofer Project Group Translational Medicine & Pharmacology at the Goethe University), H.B. received funding from Pfizer Pharma, Germany (Forschungsfo ̈ rderpreis Rheumatologie 2012). Support for the Australian component of the study was received from Abbvie Plc. MAB is funded by an National Health and Medical Research Foundation (Australia) Senior Principal Research Fellowship. C.W. is funded by the Wellcome Trust (089989) and supported by grants awarded to the Diabetes and Inflammation Laboratory from JDRF (9-2011-253) and Wellcome Trust (091157). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).
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Full list of authors on original publication

Ross Mcmanus, Gary Donohoe

Experts in our system

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Ross Mcmanus
Trinity College Dublin
 
2
Gary Donohoe
Trinity College Dublin
Total Publications: 130