Genetic variants at CD28, PRDM1, and CD2/CD58 are associated with rheumatoid arthritis risk

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Abstract

To discover novel RA risk loci, we systematically examined 370 SNPs from 179 independent loci with p<0.001 in a published meta-analysis of RA GWAS of 3,393 cases and 12,462 controls ¹. We used GRAIL ², a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci ^{1,
3-
11}. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three validate convincingly: CD2/CD58 (rs11586238, p=1×10 ⁻⁶ replication, p=1×10 ⁻⁹ overall), and CD28 (rs1980422, p=5×10 ⁻⁶ replication, p=1×10 ⁻⁹ overall), PRDM1 (rs548234, p=1×10 ⁻⁵ replication, p=2×10 ⁻⁸ overall). An additional four replicate ( p<0.0023): TAGAP (rs394581, p=0.0002 replication, p=4×10 ⁻⁷ overall), PTPRC (rs10919563, p=0.0003 replication, p=7×10 ⁻⁷ overall), TRAF6/RAG1 (rs540386, p=0.0008 replication, p=4×10 ⁻⁶ overall), and FCGR2A (rs12746613, p=0.0022 replication, p=2×10 ⁻⁵ overall). Many of these loci are also associated to other immunologic diseases.

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Most cited references 34

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The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

D McShane, D. Bloch, Emma Healey … (1988)

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

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Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.

Christopher Amos, Xifeng Wu, Peter Broderick … (2008)

To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.

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The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.

P K Gregersen, J. Silver, R Winchester (1987)

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Author and article information

Journal

Journal ID (nlm-journal-id): 9216904

Journal ID (pubmed-jr-id): 2419

Journal ID (nlm-ta): Nat Genet

Journal ID (iso-abbrev): Nat. Genet.

Title: Nature genetics

ISSN (Print): 1061-4036

ISSN (Electronic): 1546-1718

Publication date Nihms-submitted: 13 May 2010

Publication date (Electronic): 08 November 2009

Publication date (Print): December 2009

Publication date PMC-release: 25 July 2011

Volume: 41

Issue: 12

Pages: 1313-1318

Affiliations

[1 ]Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, Massachusetts, 02115, USA.

[2 ]Broad Institute, Cambridge, Massachusetts, 02142 USA

[3 ]Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.

[4 ]Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.

[5 ]Arthritis Research Campaign (arc)–Epidemiology Unit, Stopford Building, The University of Manchester, Manchester M13 9PT, United Kingdom.

[6 ]Celera, Alameda, California 94502, USA.

[7 ]Dept of Medicine, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, Ontario M5G 1X5, Canada.

[8 ]Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden.

[9 ]University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

[10 ]Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California 94143, USA.

[11 ]Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.

[12 ]Department of Neurology, Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA.

[13 ]NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, LS9 7TF, United Kingdom.

[14 ]University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, United Kingdom.

[15 ]Musculoskeletal and Genetics Section, Division of Applied Medicine, University of Aberdeen, AB25 2ZD, United Kingdom.

[16 ]Department of Rheumatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands.

[17 ]The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA.

[18 ]Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm 171 76, Sweden.

[19 ]Genome Institute of Singapore, Singapore 138672.

[20 ]Rowe Program in Genetics, University of California at Davis, Davis, California 95616, USA.

[21 ]Clinical and Academic Rheumatology, Kings College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, United Kingdom.

[22 ]Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands.

[23 ]Department of Rheumatology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.

[24 ]School of Medicine & Biomedical Sciences, Sheffield University, Sheffield S10 2JF, United Kingdom.

[25 ]Jan van Breemen Institute, 1056 AB Amsterdam, The Netherlands.

[26 ]Sanquin Research Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1006 AD Amsterdam, The Netherlands.

[27 ]Roche Diagnostics, Pleasanton, CA 94588 USA.

Author notes

[†† ]Corresponding authors

CONTRIBUTIONS SR, MJD, DA, and RMP designed the study, conducted the statistical analysis, interpreted the primary data, and wrote the initial manuscript. All authors contributed to the final manuscript. BPT, EFR, SE, AH, CG, JJC, GX, EAS, RC, NPB, MS were involved directly in genotyping samples or extracting genotypes for this study. The BRASS genetic study was coordinated by EAS, PLdJ, JC, SR, and RMP under the direction of MEW and NAS. The CANADA genetic study was coordinated by CIA, XL, and GX under the direction of KAS. The EIRA genetic study was coordinated by LA, BD, LP, and MS under the direction of LK. The GCI genetic study was coordinated by KGA, JJC, MC, and YL under the direction of ABB. The GENRA genetic study was coordinated by JBAC, PPT, IEvdH-B, GJW under the direction of NdV. The LUMC genetic study was coordinated by TWJH, FASK, YL, AHMvdH-vM, under the direction of REMT. The NARAC genetic study was coordinated by EFR, CIA, MC, LAC, DLK, ATL, MFS, under the direction of PKG. The NHS genetic study was coordinated by KHC and JC under the direction of EWK. The UKRAG genetic study was coordinated by SE, BIRAC, AB, JB, PE, EF, PH, AH, LJH, XK, PM, AWM, DMR, SS, WT, AGW, PW, and YEAR under the direction of JW.

[†]

Supplementary Note Online

Article

Manuscript ID: nihpa150769

DOI: 10.1038/ng.479

PMC ID: 3142887

PubMed ID: 19898481

SO-VID: 99561ae3-9b51-4b8a-b2f6-76a7dd629635