OBJECTIVE: Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study. METHODS: Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation. RESULTS: A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline. CONCLUSION: Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.
OBJECTIVE: Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study. METHODS: Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation. RESULTS: A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline. CONCLUSION: Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.
Authors: X Wu; V Kondragunta; K S Kornman; H Y Wang; G W Duff; J B Renner; J M Jordan Journal: Osteoarthritis Cartilage Date: 2013-04-18 Impact factor: 6.576
Authors: Dana L Duren; Richard J Sherwood; Stefan A Czerwinski; William Cameron Chumlea; Miryoung Lee; Ellen W Demerath; Shumei S Sun; Roger M Siervogel; Bradford Towne Journal: Hum Biol Date: 2008-02 Impact factor: 0.553
Authors: Evangelos Evangelou; Ana M Valdes; Hanneke J M Kerkhof; Unnur Styrkarsdottir; Yanyan Zhu; Ingrid Meulenbelt; Rik J Lories; Fotini B Karassa; Przemko Tylzanowski; Steffan D Bos; Toru Akune; Nigel K Arden; Andrew Carr; Kay Chapman; L Adrienne Cupples; Jin Dai; Panos Deloukas; Michael Doherty; Sally Doherty; Gunnar Engstrom; Antonio Gonzalez; Bjarni V Halldorsson; Christina L Hammond; Deborah J Hart; Hafdis Helgadottir; Albert Hofman; Shiro Ikegawa; Thorvaldur Ingvarsson; Qing Jiang; Helgi Jonsson; Jaakko Kaprio; Hiroshi Kawaguchi; Kalle Kisand; Margreet Kloppenburg; Urho M Kujala; L Stefan Lohmander; John Loughlin; Frank P Luyten; Akihiko Mabuchi; Andrew McCaskie; Masahiro Nakajima; Peter M Nilsson; Nao Nishida; William E R Ollier; Kalliope Panoutsopoulou; Tom van de Putte; Stuart H Ralston; Fernado Rivadeneira; Janna Saarela; Stefan Schulte-Merker; Dongquan Shi; P Eline Slagboom; Akihiro Sudo; Agu Tamm; Ann Tamm; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Aspasia Tsezou; Gillian A Wallis; J Mark Wilkinson; Noriko Yoshimura; Eleftheria Zeggini; Guangju Zhai; Feng Zhang; Ingileif Jonsdottir; Andre G Uitterlinden; David T Felson; Joyce B van Meurs; Kari Stefansson; John P A Ioannidis; Timothy D Spector Journal: Ann Rheum Dis Date: 2010-11-10 Impact factor: 19.103
Authors: Mukundan Attur; Hwa-Ying Wang; Virginia Byers Kraus; Jack F Bukowski; Nazneen Aziz; Svetlana Krasnokutsky; Jonathan Samuels; Jeffrey Greenberg; Gary McDaniel; Steven B Abramson; Kenneth S Kornman Journal: Ann Rheum Dis Date: 2009-11-23 Impact factor: 19.103