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Published in: Rheumatology International 11/2006

01-09-2006 | Review

Osteoarthritis susceptibility loci defined by genome scan meta-analysis

Authors: Young Ho Lee, Young Hee Rho, Seong Jae Choi, Jong Dae Ji, Gwan Gyu Song

Published in: Rheumatology International | Issue 11/2006

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Abstract

Genome scans for osteoarthritis (OA) have yielded inconsistent results. The absence of replication of linkage might be due to lack of power of individual studies. A meta-analysis of the published data was performed to assess evidence for linkage of OA across genome scan studies. Three OA whole-genome scans including 893 families with 3,000 affected individuals were used for genome scan meta-analysis (GSMA). A total of 5 bins lie above 95% confidence level (P = 0.05) and 1 bin is above 99% confidence level (P = 0.01) in OA GSMA; bins 7.6 (7q34–7q36.3, Psumrnk = 0.0035), 11.3 (11p12–11q13.4), 6.3 (6p21.1–6q15), 2.8 (2q31.1–2q34) and 15.3 (15q21.3–15q26.1). The highest summed rank was observed at bin 7.6. In conclusion, the OA GSMA has shown chromosome 7q34–7q36.3 with the highest summed rank and four additional loci with significant summed ranks across studies.
Literature
1.
2.
go back to reference Loughlin J (2002) Genome studies and linkage in primary osteoarthritis. Rheum Dis Clin North Am 28:95–109PubMedCrossRef Loughlin J (2002) Genome studies and linkage in primary osteoarthritis. Rheum Dis Clin North Am 28:95–109PubMedCrossRef
3.
go back to reference Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D (1996) Genetic influences on osteoarthritis in women: a twin study. BMJ 312:940–943PubMed Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D (1996) Genetic influences on osteoarthritis in women: a twin study. BMJ 312:940–943PubMed
4.
go back to reference Sambrook PN, MacGregor AJ, Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42:366–372PubMedCrossRef Sambrook PN, MacGregor AJ, Spector TD (1999) Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 42:366–372PubMedCrossRef
5.
go back to reference Chitnavis J, Sinsheimer JS, Clipsham K, Loughlin J, Sykes B, Burge PD, Carr AJ (1997) Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg Br 79:660–664PubMedCrossRef Chitnavis J, Sinsheimer JS, Clipsham K, Loughlin J, Sykes B, Burge PD, Carr AJ (1997) Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg Br 79:660–664PubMedCrossRef
6.
go back to reference Hirsch R, Lethbridge-Cejku M, Hanson R, Scott WW Jr, Reichle R, Plato CC, Tobin JD, Hochberg MC (1998) Familial aggregation of osteoarthritis: data from the Baltimore longitudinal study on aging. Arthritis Rheum 41:1227–1232PubMedCrossRef Hirsch R, Lethbridge-Cejku M, Hanson R, Scott WW Jr, Reichle R, Plato CC, Tobin JD, Hochberg MC (1998) Familial aggregation of osteoarthritis: data from the Baltimore longitudinal study on aging. Arthritis Rheum 41:1227–1232PubMedCrossRef
7.
go back to reference Lanyon P, Muir K, Doherty S, Doherty M (2000) Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. BMJ 321:1179–1183PubMedCrossRef Lanyon P, Muir K, Doherty S, Doherty M (2000) Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. BMJ 321:1179–1183PubMedCrossRef
8.
go back to reference Loughlin J, Mustafa Z, Smith A, Irven C, Carr AJ, Clipsham K, Chitnavis J, Bloomfield VA, McCartney M, Cox O, Sinsheimer JS, Sykes B, Chapman KE (2000) Linkage analysis of chromosome 2q in osteoarthritis. Rheumatology (Oxford) 39:377–381CrossRef Loughlin J, Mustafa Z, Smith A, Irven C, Carr AJ, Clipsham K, Chitnavis J, Bloomfield VA, McCartney M, Cox O, Sinsheimer JS, Sykes B, Chapman KE (2000) Linkage analysis of chromosome 2q in osteoarthritis. Rheumatology (Oxford) 39:377–381CrossRef
9.
go back to reference Chapman K, Mustafa Z, Irven C, Carr AJ, Clipsham K, Smith A, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Cardon LR, Sykes B, Loughlin J (1999) Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage. Am J Hum Genet 65:167–174PubMedCrossRef Chapman K, Mustafa Z, Irven C, Carr AJ, Clipsham K, Smith A, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Cardon LR, Sykes B, Loughlin J (1999) Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage. Am J Hum Genet 65:167–174PubMedCrossRef
10.
go back to reference Stefansson SE, Jonsson H, Ingvarsson T, Manolescu I, Jonsson HH, Olafsdottir G, Palsdottir E, Stefansdottir G, Sveinbjornsdottir G, Frigge ML, Kong A, Gulcher JR, Stefansson K (2003) Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3. Am J Hum Genet 72:1448–1459PubMedCrossRef Stefansson SE, Jonsson H, Ingvarsson T, Manolescu I, Jonsson HH, Olafsdottir G, Palsdottir E, Stefansdottir G, Sveinbjornsdottir G, Frigge ML, Kong A, Gulcher JR, Stefansson K (2003) Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3. Am J Hum Genet 72:1448–1459PubMedCrossRef
11.
go back to reference Hunter DJ, Demissie S, Cupples LA, Aliabadi P, Felson DT (2004) A genome scan for joint-specific hand osteoarthritis susceptibility: the Framingham study. Arthritis Rheum 50:2489–2496PubMedCrossRef Hunter DJ, Demissie S, Cupples LA, Aliabadi P, Felson DT (2004) A genome scan for joint-specific hand osteoarthritis susceptibility: the Framingham study. Arthritis Rheum 50:2489–2496PubMedCrossRef
12.
go back to reference Levinson DF, Levinson MD, Segurado R, Lewis CM (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: methods and power analysis. Am J Hum Genet 73:17–33PubMedCrossRef Levinson DF, Levinson MD, Segurado R, Lewis CM (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: methods and power analysis. Am J Hum Genet 73:17–33PubMedCrossRef
13.
go back to reference Demissie S, Cupples LA, Myers R, Aliabadi P, Levy D, Felson DT (2002) Genome scan for quantity of hand osteoarthritis: the Framingham study. Arthritis Rheum 46:946–952PubMedCrossRef Demissie S, Cupples LA, Myers R, Aliabadi P, Levy D, Felson DT (2002) Genome scan for quantity of hand osteoarthritis: the Framingham study. Arthritis Rheum 46:946–952PubMedCrossRef
14.
go back to reference Wright GD, Hughes AE, Regan M, Doherty M (1996) Association of two loci on chromosome 2q with nodal osteoarthritis. Ann Rheum Dis 55:317–319PubMedCrossRef Wright GD, Hughes AE, Regan M, Doherty M (1996) Association of two loci on chromosome 2q with nodal osteoarthritis. Ann Rheum Dis 55:317–319PubMedCrossRef
15.
go back to reference Southam L, Dowling B, Ferreira A, Marcelline L, Mustafa Z, Chapman K, Bentham G, Carr A, Loughlin J (2004) Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3–q13. Arthritis Rheum 50:3910–3914PubMedCrossRef Southam L, Dowling B, Ferreira A, Marcelline L, Mustafa Z, Chapman K, Bentham G, Carr A, Loughlin J (2004) Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3–q13. Arthritis Rheum 50:3910–3914PubMedCrossRef
16.
go back to reference Mustafa Z, Chapman K, Irven C, Carr AJ, Clipsham K, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Sykes B, Loughlin J (2000) Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis. Rheumatology (Oxford) 39:299–306CrossRef Mustafa Z, Chapman K, Irven C, Carr AJ, Clipsham K, Chitnavis J, Sinsheimer JS, Bloomfield VA, McCartney M, Cox O, Sykes B, Loughlin J (2000) Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis. Rheumatology (Oxford) 39:299–306CrossRef
17.
go back to reference Forster T, Chapman K, Marcelline L, Mustafa Z, Southam L, Loughlin J (2004) Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women. Arthritis Rheum 50:98–102PubMedCrossRef Forster T, Chapman K, Marcelline L, Mustafa Z, Southam L, Loughlin J (2004) Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women. Arthritis Rheum 50:98–102PubMedCrossRef
18.
go back to reference Leppavuori J, Kujala U, Kinnunen J, Kaprio J, Nissila M, Heliovaara M, Klinger N, Partanen J, Terwilliger JD, Peltonen L (1999) Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locs on 2q. Am J Hum Genet 65:1060–1067PubMedCrossRef Leppavuori J, Kujala U, Kinnunen J, Kaprio J, Nissila M, Heliovaara M, Klinger N, Partanen J, Terwilliger JD, Peltonen L (1999) Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locs on 2q. Am J Hum Genet 65:1060–1067PubMedCrossRef
19.
go back to reference Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M (2001) Genomewide scans of complex human diseases: true linkage is hard to find. Am J Hum Genet 69:936–950PubMedCrossRef Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M (2001) Genomewide scans of complex human diseases: true linkage is hard to find. Am J Hum Genet 69:936–950PubMedCrossRef
20.
go back to reference Goring HH, Terwilliger JD, Blangero J (2001) Large upward bias in estimation of locus-specific effects from genomewide scans. Am J Hum Genet 69:1357–1369PubMedCrossRef Goring HH, Terwilliger JD, Blangero J (2001) Large upward bias in estimation of locus-specific effects from genomewide scans. Am J Hum Genet 69:1357–1369PubMedCrossRef
21.
go back to reference Usdin TB, Modi W, Bonner TI (1996) Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics 37:140–141PubMedCrossRef Usdin TB, Modi W, Bonner TI (1996) Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics 37:140–141PubMedCrossRef
22.
go back to reference Usdin TB, Gruber C, Bonner TI (1995) Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem 270:15455–15458PubMedCrossRef Usdin TB, Gruber C, Bonner TI (1995) Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem 270:15455–15458PubMedCrossRef
23.
go back to reference Wright GD, Hughes AE, Regan M, Doherty M (1996) Association of two loci on chromosome 2q with nodal osteoarthritis. Ann Rheum Dis 55:317–319PubMed Wright GD, Hughes AE, Regan M, Doherty M (1996) Association of two loci on chromosome 2q with nodal osteoarthritis. Ann Rheum Dis 55:317–319PubMed
24.
25.
go back to reference Lane NE, Nevitt MC (1994) Osteoarthritis and bone mass. J Rheumatol 21:1393–1396PubMed Lane NE, Nevitt MC (1994) Osteoarthritis and bone mass. J Rheumatol 21:1393–1396PubMed
26.
go back to reference Kellgren JH, Moore R (1952) Generalized osteoarthritis and Heberden’s nodes. Br Med J 1:181–187PubMedCrossRef Kellgren JH, Moore R (1952) Generalized osteoarthritis and Heberden’s nodes. Br Med J 1:181–187PubMedCrossRef
27.
go back to reference Loughlin J, Dowling B, Chapman K, Marcelline L, Mustafa Z, Southam L, Ferreira A, Ciesielski C, Carson DA, Corr M (2004) Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci USA 101:9757–9762PubMedCrossRef Loughlin J, Dowling B, Chapman K, Marcelline L, Mustafa Z, Southam L, Ferreira A, Ciesielski C, Carson DA, Corr M (2004) Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci USA 101:9757–9762PubMedCrossRef
Metadata
Title
Osteoarthritis susceptibility loci defined by genome scan meta-analysis
Authors
Young Ho Lee
Young Hee Rho
Seong Jae Choi
Jong Dae Ji
Gwan Gyu Song
Publication date
01-09-2006
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 11/2006
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-006-0181-9

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