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Pregled bibliografske jedinice broj: 728047

Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study


Zeggini, E.; Panoutsopoulou, K.; Southam, L.; Rayner, N.W.; Day-Williams, A.G.; Lopes, M.C.; Boraska, Vesna; Esko, T.; Evangelou, E.; Hoffman, A. et al.
Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study // The Lancet, 380 (2012), 9844; 815-823 doi:10.1016/S0140-6736(12)60681-3 (međunarodna recenzija, članak, znanstveni)


Naslov
Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study

Autori
Zeggini, E. ; Panoutsopoulou, K. ; Southam, L. ; Rayner, N.W. ; Day-Williams, A.G. ; Lopes, M.C. ; Boraska, Vesna ; Esko, T. ; Evangelou, E. ; Hoffman, A. ; Houwing-Duistermaat, J.J. ; Ingvarsson, T. ; Jonsdottir, I. ; Jonnson, H. ; Kerkhof, H.J. ; Kloppenburg, M. ; Bos, S.D. ; Mangino, M. ; Metrustry, S.V. ; Ratnayake, M ; Ricketts, M. ; Beazley, C. ; Blackburn, H. ; Bumpstead, S. ; Elliott, K.S. ; Hunt, S.E. ; Potter, S.C. ; Shin, S.Y. ; Yadav, V.K. ; Zhai, G. ; Sherburn, K. ; Dixon, K. ; Arden, E. ; Aslam, N. ; Battley, P.K. ; Carluke, I. ; Doherty, S. ; Gordon, A. ; Joseph, J. ; Keen, R. ; Koller, N.C. ; Mitchell, S. ; O'Neill, F. ; Paling, E. ; Reed, M.R. ; Rivadeneira, F. ; Swift, D. ; Walker, K. ; Watkins, B. ; Wheeler, M. ; Birrell, F. ; Ioannidis, J.P. ; Meulenbelt, I. ; Metspalu, A. ; Rai, A. ; Salter, D. ; Stefansson, K. ; Stykarsdottir, U. ; Uitterlinden, A.G. ; van Meurs, J.B. ; Chapman, K. ; Deloukas, P. ; Ollier, W.E. ; Wallis, G.A. ; Arden, N. ; Carr, A. ; Doherty, M. ; McCaskie, A. ; Willkinson, J.M. ; Ralston, S.H. ; Valdes, A.M. ; Spector, T.D. ; Loughlin, J.

Izvornik
The Lancet (0140-6736) 380 (2012), 9844; 815-823

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Osteoarthritis; GWAS

Sažetak
Background Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insuffi cient sample sizes and phenotype heterogeneity. Methods We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11 009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42 938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. Findings We identifi ed fi ve genome-wide signifi cant loci (binomial test p≤5·0×10–⁸) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08–1·16] ; p=7·24×10–¹¹), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other signifi cant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide signifi cance was within the FTO gene, which is involved in regulation of bodyweight—a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small eff ects. Interpretation Our fi ndings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

Napomena
ArcOGEN Consortium ; arcOGEN Collaborators.



POVEZANOST RADA


Projekt / tema
HRZZ-PD-02.03/68 - Analiza i interpretacija cjelogenomskih studija povezanosti: primjena u projektu 10,001 Dalmatinac (Vesna Boraska, )

Ustanove
Medicinski fakultet, Split

Autor s matičnim brojem:
Vesna Boraska, (276771)

Citiraj ovu publikaciju

Zeggini, E.; Panoutsopoulou, K.; Southam, L.; Rayner, N.W.; Day-Williams, A.G.; Lopes, M.C.; Boraska, Vesna; Esko, T.; Evangelou, E.; Hoffman, A. et al.
Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study // The Lancet, 380 (2012), 9844; 815-823 doi:10.1016/S0140-6736(12)60681-3 (međunarodna recenzija, članak, znanstveni)
Zeggini, E., Panoutsopoulou, K., Southam, L., Rayner, N., Day-Williams, A., Lopes, M., Boraska, V., Esko, T., Evangelou, E. & Hoffman, A. (2012) Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. The Lancet, 380 (9844), 815-823 doi:10.1016/S0140-6736(12)60681-3.
@article{article, year = {2012}, pages = {815-823}, DOI = {10.1016/S0140-6736(12)60681-3}, keywords = {osteoarthritis, GWAS}, journal = {The Lancet}, doi = {10.1016/S0140-6736(12)60681-3}, volume = {380}, number = {9844}, issn = {0140-6736}, title = {Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study}, keyword = {osteoarthritis, GWAS} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • MEDLINE


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