title: Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis.
abstract: 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.
authors: Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK.
authors: John
authors: J
authors: Bowes
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester M13 9WU, UK.
authors: Ashley
authors: A
authors: Budu-Aggrey
authors: Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors: Ulrike
authors: U
authors: Huffmeier
authors: Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors: Steffen
authors: S
authors: Uebe
authors: Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK.
authors: Kathryn
authors: K
authors: Steel
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK.
authors: Harry L
authors: HL
authors: Hebert
authors: 1] JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK [2] Centre for Biostatistics, Institute of Population Health, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester M13 9PL, UK.
authors: Chris
authors: C
authors: Wallace
authors: Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK.
authors: Jonathan
authors: J
authors: Massey
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester M13 9WL, UK.
authors: Ian N
authors: IN
authors: Bruce
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester M13 9WL, UK.
authors: James
authors: J
authors: Bluett
authors: Monash University, Melbourne, Victoria 3800, Australia.
authors: Marie
authors: M
authors: Feletar
authors: NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK.
authors: Ann W
authors: AW
authors: Morgan
authors: NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK.
authors: Helena
authors: H
authors: Marzo-Ortega
authors: CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland, Galway, Ireland.
authors: Gary
authors: G
authors: Donohoe
authors: CogGene Group, Discipline of Biochemistry and School of Psychology, National University of Ireland, Galway, Ireland.
authors: Derek W
authors: DW
authors: Morris
authors: NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK.
authors: Philip
authors: P
authors: Helliwell
authors: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
authors: Anthony W
authors: AW
authors: Ryan
authors: Adelaide and Meath Hospital and Trinity College Dublin, Dublin 24, Ireland.
authors: David
authors: D
authors: Kane
authors: The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, UK.
authors: Richard B
authors: RB
authors: Warren
authors: Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath BA1 1RL, UK.
authors: Eleanor
authors: E
authors: Korendowych
authors: Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, Umeå 901 87, Sweden.
authors: Gerd-Marie
authors: GM
authors: Alenius
authors: Department of Biopathology, Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, School of Medicine, University of Rome 'Tor Vergata' and Fondazione PTV 'Policlinico Tor Vergata', Rome 18-00173, Italy.
authors: Emiliano
authors: E
authors: Giardina
authors: Rheumatology Department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University, Keele ST5 5BG, UK.
authors: Jonathan
authors: J
authors: Packham
authors: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
authors: Ross
authors: R
authors: McManus
authors: Department of Rheumatology, St. Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
authors: Oliver
authors: O
authors: FitzGerald
authors: Royal National Hospital for Rheumatic Diseases and Department of Pharmacy and Pharmacology, University of Bath, Bath BA1 1RL, UK.
authors: Neil
authors: N
authors: McHugh
authors: The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland QLD 4102, Australia.
authors: Matthew A
authors: MA
authors: Brown
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester M13 9WL, UK.
authors: Pauline
authors: P
authors: Ho
authors: Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt 60590, Germany.
authors: Frank
authors: F
authors: Behrens
authors: Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt 60590, Germany.
authors: Harald
authors: H
authors: Burkhardt
authors: Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
authors: Andre
authors: A
authors: Reis
authors: 1] Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester M13 9PT, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester M13 9WU, UK.
authors: Anne
authors: A
authors: Barton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002843:Chromatin / Q000737:chemistry / Q000276:immunology; D002895:Chromosomes, Human, Pair 5; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D040641:Quantitative Trait Loci / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology
chemical_list: D002843:Chromatin; D015395:Histocompatibility Antigens Class I; C515500:IL23R protein, human; D018123:Receptors, Interleukin
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