A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22
dc.creator | Kerkhof, H. J. M. | en |
dc.creator | Lories, R. J. | en |
dc.creator | Meulenbelt, I. | en |
dc.creator | Jonsdottir, I. | en |
dc.creator | Valdes, A. M. | en |
dc.creator | Arp, P. | en |
dc.creator | Ingvarsson, T. | en |
dc.creator | Jhamai, M. | en |
dc.creator | Jonsson, H. | en |
dc.creator | Stolk, L. | en |
dc.creator | Thorleifsson, G. | en |
dc.creator | Zhai, G. | en |
dc.creator | Zhang, F. | en |
dc.creator | Zhu, Y. | en |
dc.creator | Van Der Breggen, R. | en |
dc.creator | Carr, A. | en |
dc.creator | Doherty, M. | en |
dc.creator | Doherty, S. | en |
dc.creator | Felson, D. T. | en |
dc.creator | Gonzalez, A. | en |
dc.creator | Halldorsson, B. V. | en |
dc.creator | Hart, D. J. | en |
dc.creator | Hauksson, V. B. | en |
dc.creator | Hofman, A. | en |
dc.creator | Ioannidis, J. P. A. | en |
dc.creator | Kloppenburg, M. | en |
dc.creator | Lane, N. E. | en |
dc.creator | Loughlin, J. | en |
dc.creator | Luyten, F. P. | en |
dc.creator | Nevitt, M. C. | en |
dc.creator | Parimi, N. | en |
dc.creator | Pols, H. A. P. | en |
dc.creator | Rivadeneira, F. | en |
dc.creator | Slagboom, E. P. | en |
dc.creator | Styrḱarsd́ottir, U. | en |
dc.creator | Tsezou, A. | en |
dc.creator | Van De Putte, T. | en |
dc.creator | Zmuda, J. | en |
dc.creator | Spector, T. D. | en |
dc.creator | Stefansson, K. | en |
dc.creator | Uitterlinden, A. G. | en |
dc.creator | Van Meurs, J. B. J. | en |
dc.date.accessioned | 2015-11-23T10:34:43Z | |
dc.date.available | 2015-11-23T10:34:43Z | |
dc.date.issued | 2010 | |
dc.identifier | 10.1002/art.27184 | |
dc.identifier.issn | 43591 | |
dc.identifier.uri | http://hdl.handle.net/11615/29382 | |
dc.description.abstract | Objective. To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and ∼39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10-7 considered genomewide significant. Results. The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10-8) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10-12). Immunohistochemistry experiments revealed that G protein-coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. Conclusion. Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein-coupled receptor, this is potentially an interesting therapeutic target. © 2010, American College of Rheumatology. | en |
dc.source.uri | http://www.scopus.com/inward/record.url?eid=2-s2.0-75749110202&partnerID=40&md5=202021362a94581028cb65a97e5185cb | |
dc.subject | bovine serum albumin | en |
dc.subject | G protein coupled receptor | en |
dc.subject | G protein coupled receptor 22 | en |
dc.subject | papain | en |
dc.subject | unclassified drug | en |
dc.subject | allele | en |
dc.subject | animal experiment | en |
dc.subject | animal model | en |
dc.subject | article | en |
dc.subject | articular cartilage | en |
dc.subject | Caucasian | en |
dc.subject | chromosome 7q | en |
dc.subject | controlled study | en |
dc.subject | disease predisposition | en |
dc.subject | gene frequency | en |
dc.subject | gene linkage disequilibrium | en |
dc.subject | gene locus | en |
dc.subject | genetic association | en |
dc.subject | genome | en |
dc.subject | hand | en |
dc.subject | human | en |
dc.subject | immunohistochemistry | en |
dc.subject | knee osteoarthritis | en |
dc.subject | lymphoblast | en |
dc.subject | major clinical study | en |
dc.subject | meta analysis | en |
dc.subject | mouse | en |
dc.subject | nonhuman | en |
dc.subject | osteoarthritis | en |
dc.subject | phenotype | en |
dc.subject | priority journal | en |
dc.subject | single nucleotide polymorphism | en |
dc.subject | synovium | en |
dc.subject | Animals | en |
dc.subject | Cartilage, Articular | en |
dc.subject | Cell Line | en |
dc.subject | Chromosomes, Human, Pair 7 | en |
dc.subject | European Continental Ancestry Group | en |
dc.subject | Female | en |
dc.subject | Genetic Predisposition to Disease | en |
dc.subject | Genome-Wide Association Study | en |
dc.subject | Humans | en |
dc.subject | Lymphocytes | en |
dc.subject | Male | en |
dc.subject | Mice | en |
dc.subject | Netherlands | en |
dc.subject | Osteoarthritis, Hip | en |
dc.subject | Osteoarthritis, Knee | en |
dc.subject | Polymorphism, Single Nucleotide | en |
dc.subject | Prevalence | en |
dc.subject | Receptors, G-Protein-Coupled | en |
dc.subject | Risk Factors | en |
dc.subject | Serum Albumin, Bovine | en |
dc.subject | Synovial Membrane | en |
dc.title | A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22 | en |
dc.type | journalArticle | en |
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