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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

dc.creatorEvangelou, E.en
dc.creatorValdes, A. M.en
dc.creatorKerkhof, H. J. M.en
dc.creatorStyrkarsdottir, U.en
dc.creatorZhu, Y.en
dc.creatorMeulenbelt, I.en
dc.creatorLories, R. J.en
dc.creatorKarassa, F. B.en
dc.creatorTylzanowski, P.en
dc.creatorBos, S. D.en
dc.creatorRayner, N. W.en
dc.creatorSoutham, L.en
dc.creatorZhai, G.en
dc.creatorElliott, K. S.en
dc.creatorHunt, S. E.en
dc.creatorBlackburn, H.en
dc.creatorPotter, S. C.en
dc.creatorDay-Williams, A. G.en
dc.creatorBeazley, C.en
dc.creatorAkune, T.en
dc.creatorArden, N. K.en
dc.creatorCarr, A.en
dc.creatorChapman, K.en
dc.creatorCupples, L. A.en
dc.creatorDai, J.en
dc.creatorDeloukas, P.en
dc.creatorDoherty, M.en
dc.creatorDoherty, S.en
dc.creatorEngstrom, G.en
dc.creatorGonzalez, A.en
dc.creatorHalldorsson, B. V.en
dc.creatorHammond, C. L.en
dc.creatorHart, D. J.en
dc.creatorHelgadottir, H.en
dc.creatorHofman, A.en
dc.creatorIkegawa, S.en
dc.creatorIngvarsson, T.en
dc.creatorJiang, Q.en
dc.creatorJonsson, H.en
dc.creatorKaprio, J.en
dc.creatorKawaguchi, H.en
dc.creatorKisand, K.en
dc.creatorKloppenburg, M.en
dc.creatorKujala, U. M.en
dc.creatorLohmander, L. S.en
dc.creatorLoughlin, J.en
dc.creatorLuyten, F. P.en
dc.creatorMabuchi, A.en
dc.creatorMcCaskie, A.en
dc.creatorNakajima, M.en
dc.creatorNilsson, P. M.en
dc.creatorNishida, N.en
dc.creatorOllier, W. E. R.en
dc.creatorPanoutsopoulou, K.en
dc.creatorVan De Putte, T.en
dc.creatorRalston, S. H.en
dc.creatorRivadeneira, F.en
dc.creatorSaarela, J.en
dc.creatorSchulte-Merker, S.en
dc.creatorShi, D.en
dc.creatorSlagboom, P. E.en
dc.creatorSudo, A.en
dc.creatorTamm, A.en
dc.creatorThorleifsson, G.en
dc.creatorThorsteinsdottir, U.en
dc.creatorTsezou, A.en
dc.creatorWallis, G. A.en
dc.creatorWilkinson, J. M.en
dc.creatorYoshimura, N.en
dc.creatorZeggini, E.en
dc.creatorZhang, F.en
dc.creatorJonsdottir, I.en
dc.creatorUitterlinden, A. G.en
dc.creatorFelson, D. T.en
dc.creatorVan Meurs, J. B.en
dc.creatorStefansson, K.en
dc.creatorIoannidis, J. P. A.en
dc.creatorSpector, T. D.en
dc.date.accessioned2015-11-23T10:26:25Z
dc.date.available2015-11-23T10:26:25Z
dc.date.issued2011
dc.identifier10.1136/ard.2010.132787
dc.identifier.issn34967
dc.identifier.urihttp://hdl.handle.net/11615/27392
dc.description.abstractObjectives: Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods: A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results: With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2×10-9), thereby confirming its role as a susceptibility locus for OA. Conclusion: The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, β), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.en
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-78751703383&partnerID=40&md5=28c29c8504504e22fd54863a762039b3
dc.subjectB lymphocyte receptoren
dc.subjectB lymphocyte receptor associated protein 29en
dc.subjectcell proteinen
dc.subjectcomponent of oligomeric golgi complex 5en
dc.subjectcyclic AMP dependent protein kinase regulatory subunit IIbetaen
dc.subjectdihydrouridine synthase 4en
dc.subjectG protein coupled receptor 22en
dc.subjectguanine nucleotide binding proteinen
dc.subjectHMG box transcription factor 1en
dc.subjectsynthetaseen
dc.subjecttranscription factoren
dc.subjectunclassified drugen
dc.subjectadulten
dc.subjectarticleen
dc.subjectCaucasianen
dc.subjectchromosome 7qen
dc.subjectcontrolled studyen
dc.subjectfemaleen
dc.subjectgene expressionen
dc.subjectgene linkage disequilibriumen
dc.subjectgene locusen
dc.subjectgene replicationen
dc.subjectgenetic associationen
dc.subjectgenetic susceptibilityen
dc.subjecthumanen
dc.subjectknee osteoarthritisen
dc.subjectmajor clinical studyen
dc.subjectmaleen
dc.subjectmeta analysisen
dc.subjectpriority journalen
dc.subjectsample sizeen
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectChromosomes, Human, Pair 7en
dc.subjectGene Expression Profilingen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenome-Wide Association Studyen
dc.subjectGenotypeen
dc.subjectHumansen
dc.subjectMiddle Ageden
dc.subjectOsteoarthritis, Kneeen
dc.subjectPhenotypeen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectYoung Adulten
dc.titleMeta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22en
dc.typejournalArticleen


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