Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.

2.50
Hdl Handle:
http://hdl.handle.net/2336/82853
Title:
Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.
Authors:
Evangelou, Evangelos; Chapman, Kay; Meulenbelt, Ingrid; Karassa, Fotini B; Loughlin, John; Carr, Andrew; Doherty, Michael; Doherty, Sally; Gómez-Reino, Juan J; Gonzalez, Antonio; Halldorsson, Bjarni V; Hauksson, Valdimar B; Hofman, Albert; Hart, Deborah J; Ikegawa, Shiro; Ingvarsson, Thorvaldur; Jiang, Qing; Jonsdottir, Ingileif; Jonsson, Helgi; Kerkhof, Hanneke J M; Kloppenburg, Margreet; Lane, Nancy E; Li, Jia; Lories, Rik J; van Meurs, Joyce B J; Näkki, Annu; Nevitt, Michael C; Rodriguez-Lopez, Julio; Shi, Dongquan; Slagboom, P Eline; Stefansson, Kari; Tsezou, Aspasia; Wallis, Gillian A; Watson, Christopher M; Spector, Tim D; Uitterlinden, Andre G; Valdes, Ana M; Ioannidis, John P A
Citation:
Arthritis Rheum. 2009, 60(6):1710-21
Issue Date:
1-Jun-2009
Abstract:
OBJECTIVE: GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. METHODS: Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. RESULTS: A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09-1.22]) (P=9.4x10(-7)), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P=0.016]) or absent (for OA of the hand [P=0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P=0.019). CONCLUSION: Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1002/art.24524

Full metadata record

DC FieldValue Language
dc.contributor.authorEvangelou, Evangelosen
dc.contributor.authorChapman, Kayen
dc.contributor.authorMeulenbelt, Ingriden
dc.contributor.authorKarassa, Fotini Ben
dc.contributor.authorLoughlin, Johnen
dc.contributor.authorCarr, Andrewen
dc.contributor.authorDoherty, Michaelen
dc.contributor.authorDoherty, Sallyen
dc.contributor.authorGómez-Reino, Juan Jen
dc.contributor.authorGonzalez, Antonioen
dc.contributor.authorHalldorsson, Bjarni Ven
dc.contributor.authorHauksson, Valdimar Ben
dc.contributor.authorHofman, Alberten
dc.contributor.authorHart, Deborah Jen
dc.contributor.authorIkegawa, Shiroen
dc.contributor.authorIngvarsson, Thorvalduren
dc.contributor.authorJiang, Qingen
dc.contributor.authorJonsdottir, Ingileifen
dc.contributor.authorJonsson, Helgien
dc.contributor.authorKerkhof, Hanneke J Men
dc.contributor.authorKloppenburg, Margreeten
dc.contributor.authorLane, Nancy Een
dc.contributor.authorLi, Jiaen
dc.contributor.authorLories, Rik Jen
dc.contributor.authorvan Meurs, Joyce B Jen
dc.contributor.authorNäkki, Annuen
dc.contributor.authorNevitt, Michael Cen
dc.contributor.authorRodriguez-Lopez, Julioen
dc.contributor.authorShi, Dongquanen
dc.contributor.authorSlagboom, P Elineen
dc.contributor.authorStefansson, Karien
dc.contributor.authorTsezou, Aspasiaen
dc.contributor.authorWallis, Gillian Aen
dc.contributor.authorWatson, Christopher Men
dc.contributor.authorSpector, Tim Den
dc.contributor.authorUitterlinden, Andre Gen
dc.contributor.authorValdes, Ana Men
dc.contributor.authorIoannidis, John P Aen
dc.date.accessioned2009-09-28T13:14:42Z-
dc.date.available2009-09-28T13:14:42Z-
dc.date.issued2009-06-01-
dc.date.submitted2009-09-28-
dc.identifier.citationArthritis Rheum. 2009, 60(6):1710-21en
dc.identifier.issn0004-3591-
dc.identifier.pmid19479880-
dc.identifier.doi10.1002/art.24524-
dc.identifier.urihttp://hdl.handle.net/2336/82853-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractOBJECTIVE: GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. METHODS: Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. RESULTS: A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09-1.22]) (P=9.4x10(-7)), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P=0.016]) or absent (for OA of the hand [P=0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P=0.019). CONCLUSION: Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.en
dc.language.isoenen
dc.publisherWiley-Liss, Inc.en
dc.relation.urlhttp://dx.doi.org/10.1002/art.24524en
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshBayes Theoremen
dc.subject.meshCase-Control Studiesen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGlycoproteinsen
dc.subject.meshGrowth Differentiation Factor 5en
dc.subject.meshHand Jointsen
dc.subject.meshHaplotypesen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshOsteoarthritisen
dc.subject.meshOsteoarthritis, Hipen
dc.subject.meshOsteoarthritis, Kneeen
dc.subject.meshPhenotypeen
dc.subject.meshPolymorphism, Geneticen
dc.titleLarge-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.en
dc.typeArticleen
dc.contributor.departmentDepartment of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.en
dc.identifier.journalArthritis and rheumatismen

Related articles on PubMed

All Items in Hirsla are protected by copyright, with all rights reserved, unless otherwise indicated.