Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Rayner, Nigel W
Day-Williams, Aaron G
Lopes, Margarida C
Houwing-Duistermaat, Jeanine J
Kerkhof, Hanneke J
Bos, Steffan D
Slagboom, P Eline
Raine, Emma V A
Elliott, Katherine S
Hunt, Sarah E
Potter, Simon C
Yadav, Vijay K
Koller, Nicola C
Reed, Mike R
Ioannidis, John P A
Uitterlinden, André G
van Meurs, Joyce B J
Ollier, William E R
Wallis, Gillian A
Willkinson, J Mark
Ralston, Stuart H
Valdes, Ana M
Spector, Tim D
MetadataShow full item record
CitationLancet 2012, 380(9844):815-23
AbstractOsteoarthritis 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 insufficient sample sizes and phenotype heterogeneity. 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. We identified five genome-wide significant 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 significant 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 significance 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 effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.
DescriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.
RightsArchived with thanks to Lancet
- Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.
- Authors: Panoutsopoulou K, Southam L, Elliott KS, Wrayner N, Zhai G, Beazley C, Thorleifsson G, Arden NK, Carr A, Chapman K, Deloukas P, Doherty M, McCaskie A, Ollier WE, Ralston SH, Spector TD, Valdes AM, Wallis GA, Wilkinson JM, Arden E, Battley K, Blackburn H, Blanco FJ, Bumpstead S, Cupples LA, Day-Williams AG, Dixon K, Doherty SA, Esko T, Evangelou E, Felson D, Gomez-Reino JJ, Gonzalez A, Gordon A, Gwilliam R, Halldorsson BV, Hauksson VB, Hofman A, Hunt SE, Ioannidis JP, Ingvarsson T, Jonsdottir I, Jonsson H, Keen R, Kerkhof HJ, Kloppenburg MG, Koller N, Lakenberg N, Lane NE, Lee AT, Metspalu A, Meulenbelt I, Nevitt MC, O'Neill F, Parimi N, Potter SC, Rego-Perez I, Riancho JA, Sherburn K, Slagboom PE, Stefansson K, Styrkarsdottir U, Sumillera M, Swift D, Thorsteinsdottir U, Tsezou A, Uitterlinden AG, van Meurs JB, Watkins B, Wheeler M, Mitchell S, Zhu Y, Zmuda JM, arcOGEN Consortium., Zeggini E, Loughlin J
- Issue date: 2011 May
- A novel variant in <i>GLIS3</i> is associated with osteoarthritis.
- Authors: Casalone E, Tachmazidou I, Zengini E, Hatzikotoulas K, Hackinger S, Suveges D, Steinberg J, Rayner NW, arcOGEN Consortium., Wilkinson JM, Panoutsopoulou K, Zeggini E
- Issue date: 2018 Apr
- A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22.
- Authors: Kerkhof HJ, Lories RJ, Meulenbelt I, Jonsdottir I, Valdes AM, Arp P, Ingvarsson T, Jhamai M, Jonsson H, Stolk L, Thorleifsson G, Zhai G, Zhang F, Zhu Y, van der Breggen R, Carr A, Doherty M, Doherty S, Felson DT, Gonzalez A, Halldorsson BV, Hart DJ, Hauksson VB, Hofman A, Ioannidis JP, Kloppenburg M, Lane NE, Loughlin J, Luyten FP, Nevitt MC, Parimi N, Pols HA, Rivadeneira F, Slagboom EP, Styrkársdóttir U, Tsezou A, van de Putte T, Zmuda J, Spector TD, Stefansson K, Uitterlinden AG, van Meurs JB
- Issue date: 2010 Feb
- Large scale replication study of the association between HLA class II/BTNL2 variants and osteoarthritis of the knee in European-descent populations.
- Authors: Valdes AM, Styrkarsdottir U, Doherty M, Morris DL, Mangino M, Tamm A, Doherty SA, Kisand K, Kerna I, Tamm A, Wheeler M, Maciewicz RA, Zhang W, Muir KR, Dennison EM, Hart DJ, Metrustry S, Jonsdottir I, Jonsson GF, Jonsson H, Ingvarsson T, Cooper C, Vyse TJ, Spector TD, Stefansson K, Arden NK
- Issue date: 2011
- Functional characterisation of the osteoarthritis susceptibility locus at chromosome 6q14.1 marked by the polymorphism rs9350591.
- Authors: Johnson K, Reynard LN, Loughlin J
- Issue date: 2015 Sep 7