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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium

Kerkhof, H. J. M.; Meulenbelt, I.; Akune, T.; Arden, N. K.; Aromaa, A.; Bierma-Zeinstra, S. M. A.; Carr, A.; Cooper, C.; Dai, J. and Doherty, M., et al. (2011) In Osteoarthritis and Cartilage 19(3). p.254-264
Abstract
Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort... (More)
Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. (Less)
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keywords
Genetics, Osteoarthritis, Phenotype, Definition, TREATOA
in
Osteoarthritis and Cartilage
volume
19
issue
3
pages
254 - 264
publisher
Elsevier
external identifiers
  • wos:000288527300002
  • scopus:79951853292
ISSN
1063-4584
DOI
10.1016/j.joca.2010.10.027
language
English
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yes
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e64f516c-dcb5-4c29-b189-53960cc7b6fc (old id 1936099)
date added to LUP
2011-05-02 08:18:06
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2017-09-17 03:19:50
@article{e64f516c-dcb5-4c29-b189-53960cc7b6fc,
  abstract     = {Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.},
  author       = {Kerkhof, H. J. M. and Meulenbelt, I. and Akune, T. and Arden, N. K. and Aromaa, A. and Bierma-Zeinstra, S. M. A. and Carr, A. and Cooper, C. and Dai, J. and Doherty, M. and Doherty, S. A. and Felson, D. and Gonzalez, A. and Gordon, A. and Harilainen, A. and Hart, D. J. and Hauksson, V. B. and Heliovaara, M. and Hofman, A. and Ikegawa, S. and Ingvarsson, T. and Jiang, Q. and Jonsson, H and Jonsdottir, I. and Kawaguchi, H. and Kloppenburg, M. and Kujala, U. M. and Lane, N. E. and Leino-Arjas, P. and Lohmander, Stefan and Luyten, F. P. and Malizos, K. N. and Nakajima, M. and Nevitt, M. C. and Pols, H. A. P. and Rivadeneira, F. and Shi, D. and Slagboom, E. and Spector, T. D. and Stefansson, K. and Sudo, A. and Tamm, A. and Tamm, A. E. and Tsezou, A. and Uchida, A. and Uitterlinden, A. G. and Wilkinson, J. M. and Yoshimura, N. and Valdes, A. M. and van Meurs, J. B. J.},
  issn         = {1063-4584},
  keyword      = {Genetics,Osteoarthritis,Phenotype,Definition,TREATOA},
  language     = {eng},
  number       = {3},
  pages        = {254--264},
  publisher    = {Elsevier},
  series       = {Osteoarthritis and Cartilage},
  title        = {Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium},
  url          = {http://dx.doi.org/10.1016/j.joca.2010.10.027},
  volume       = {19},
  year         = {2011},
}