TY  - JOUR
AB  - OBJECTIVE: Osteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients. DESIGN: We compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study (EWAS) for cartilage degeneration across 170 patients and separately in 96 women and 74 men. RESULTS: We reveal widespread epigenetic differences with enrichments of nervous system and apoptosis-related processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways. CONCLUSIONS: Together, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression.
AU  - Kreitmaier, P.
AU  - Swift, D.*
AU  - Wilkinson, J.M.*
AU  - Zeggini, E.
C1  - 71297
C2  - 56030
CY  - 125 London Wall, London, England
SP  - 1126-1133
TI  - Epigenomic differences between osteoarthritis grades in primary cartilage.
JO  - Osteoarthr. Cartil.
VL  - 32
IS  - 9
PB  - Elsevier Sci Ltd
PY  - 2024
SN  - 1063-4584
ER  - 

TY  - JOUR
AB  - OBJECTIVE: Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after a knee injury and its genetic associations in UK Biobank (UKB). DESIGN: Clinically significant structural knee injuries in those ≤50 years were identified from electronic health records and self-reported data in 502,409 UKB participants. Time-to-first knee osteoarthritis (OA) code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months to 20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought. RESULTS: Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD 10.4]). Over a median of 30.2 (IQR 19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81 (1.70,1.93), P = 8.9 × 10-74. Female sex and increasing age at injury were associated with knee OA following injury (HR 1.15 [1.02,1.30];1.07 [1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR 3.26 [2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43 [0.02,8.41]). CONCLUSIONS: Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA.
AU  - Hollis, B.*
AU  - Chatzigeorgiou, C.*
AU  - Southam, L.
AU  - Hatzikotoulas, K.
AU  - Kluzek, S.*
AU  - Williams, A.*
AU  - Zeggini, E.
AU  - Jostins-Dean, L.*
AU  - Watt, F.E.*
C1  - 67873
C2  - 54351
SP  - 1377-1387
TI  - Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank.
JO  - Osteoarthr. Cartil.
VL  - 31
IS  - 10
PY  - 2023
SN  - 1063-4584
ER  - 

TY  - JOUR
AB  - OBJECTIVE: Spinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques. DESIGN: We applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified. RESULTS: Our analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10-21), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10-3) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10-6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10-7), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10-7), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10-11). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (ORallOA = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR. CONCLUSIONS: Genetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.
AU  - Sobczyk, M.K.*
AU  - Faber, B.G.*
AU  - Southam, L.
AU  - Frysz, M.*
AU  - Hartley, A.*
AU  - Zeggini, E.
AU  - Tang, H.*
AU  - Gaunt, T.R.*
C1  - 69021
C2  - 53806
CY  - 125 London Wall, London, England
SP  - 719-729
TI  - Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation.
JO  - Osteoarthr. Cartil.
VL  - 32
IS  - 6
PB  - Elsevier Sci Ltd
PY  - 2023
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Katsoula, G.
AU  - Steinberg, J.
AU  - Tuerlings, M.*
AU  - de Almeida, R.C.*
AU  - Southam, L.
AU  - Swift, D.*
AU  - Meulenbelt, I.*
AU  - Wilkinson, J.M.*
AU  - Zeggini, E.
C1  - 64845
C2  - 52166
SP  - S352-S352
TI  - A molecular map of long non-coding RNA expression, isoform switching and alternative splicing in osteoarthritis.
JO  - Osteoarthr. Cartil.
VL  - 30
PY  - 2022
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Hartley, A.*
AU  - Sanderson, E.*
AU  - Granell, R.*
AU  - Paternoster, L.*
AU  - Zheng, J.*
AU  - Southam, L.
AU  - Zeggini, E.
AU  - Gregson, C.L.*
AU  - Tobias, J.H.*
C1  - 59284
C2  - 48713
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S402-S402
TI  - Using multivariable mendelian randomization to estimate the BMI-independent causal effect of bone mineral density on osteoarthritis.
JO  - Osteoarthr. Cartil.
VL  - 28
PB  - Elsevier Sci Ltd
PY  - 2020
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Hatzikotoulas, K.
AU  - Boer, C.*
AU  - Southam, L.
AU  - Stefansdottir, L.*
AU  - Zhang, Y.*
AU  - de Almeida, R.*
AU  - Zheng, J.*
AU  - Barysenska, A.
AU  - Meulenbelt, I.*
AU  - Styrkarsdottir, U.*
AU  - van Meurs, J.*
AU  - Lee, M.*
AU  - Zeggini, E.
C1  - 59286
C2  - 48712
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S54-S54
TI  - Large-scale genome-wide meta-anaysis provide insights for the development of new disease modifying targets for osteoarthritis.
JO  - Osteoarthr. Cartil.
VL  - 28
PB  - Elsevier Sci Ltd
PY  - 2020
SN  - 1063-4584
ER  - 

TY  - JOUR
AB  - ObjectiveThis
       UK-wide OATech+ Network consensus study utilised a Delphi approach to 
      discern levels. of awareness across an expert panel regarding the role 
      of existing and novel technologies in osteoarthritis research. To direct
       future cross-disciplinary research it aimed to identify which could be 
      adopted to subcategorise patients with osteoarthritis (OA).DesignAn
       online questionnaire was formulated based on technologies which might 
      aid OA research and subcategorisation. During a two-day face-to-face 
      meeting concordance of expert opinion was established with surveys (23 
      questions) before, during and at the end of the meeting (Rounds 1,2 and 
      3, respectively). Experts spoke on current evidence for imaging, 
      genomics, epigenomics, proteomics, metabolomics, biomarkers, activity 
      monitoring, clinical engineering and machine learning relating to 
      subcategorisation. For each round of voting, ≥80% votes led to consensus
       and ≤20% to exclusion of a statement.ResultsPanel
       members were unanimous that a combination of novel technological 
      advances have potential to improve OA diagnostics and treatment through 
      subcategorisation,. agreeing in Rounds 1 and 2 that epigenetics, 
      genetics, MRI, proteomics, wet biomarkers and machine learning could aid
       subcategorisation. Expert presentations changed participants’ opinions 
      on the value of metabolomics, activity monitoring and clinical 
      engineering, all reaching consensus in Round 2. X-rays lost consensus 
      between Rounds 1 and 2; clinical X-rays reached consensus in Round 3.ConclusionConsensus
       identified that 9 of the 11 technologies should be targeted towards OA 
      subcategorisation to address existing OA research technology and 
      knowledge gaps. These novel, rapidly evolving technologies are 
      recommended as a focus for emergent, cross-disciplinary osteoarthritis 
      research programmes.
AU  - Mennan, C.*
AU  - Hopkins, T.*
AU  - Channon, A.*
AU  - Elliott, A.*
AU  - Johnstone, B.*
AU  - Kadir, T.*
AU  - Loughlin, J.*
AU  - Peffers, M.*
AU  - Pitsillides, A.*
AU  - Sofat, N.*
AU  - Stewart, C.*
AU  - Watt, F.E.*
AU  - Zeggini, E.
AU  - Holt, C.*
AU  - Roberts, S.*
C1  - 59448
C2  - 48819
TI  - The use of technology in the subcategorisation of osteoarthritis: A delphi study approach.
JO  - Osteoarthr. Cartil.
VL  - 2
IS  - 3
PY  - 2020
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Sedaghati-Khayat, B.*
AU  - Boer, C.G.*
AU  - Broer, L.*
AU  - Verkerk, A.O.*
AU  - Zeggini, E.
AU  - van Rooij, J.G.J.*
AU  - Uitterlinden, A.G.*
AU  - van Meurs, J.B.*
C1  - 59225
C2  - 48673
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S24-S24
TI  - Polygenic risk score and its potential to improve diagnostic ability in knee and hip osteoarthritis.
JO  - Osteoarthr. Cartil.
VL  - 28
PB  - Elsevier Sci Ltd
PY  - 2020
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Hatzikotoulas, K.
AU  - Tachmazidou, I.*
AU  - Southam, L.
AU  - Esparza-Gordillo, J.*
AU  - Haberland, V.*
AU  - Zheng, J.*
AU  - Johnson, T.*
AU  - Koprulu, M.*
AU  - Zengini, E.*
AU  - Steinberg, J.*
AU  - Wilkinson, J.*
AU  - Bhatnagar, S.*
AU  - Hoffmann, J.*
AU  - Buchan, N.*
AU  - Suveges, D.*
AU  - Yerges-Armstrong, L.*
AU  - Davey Smith, G.*
AU  - Gaunt, T.*
AU  - Scott, R.*
AU  - McCarthy, L.*
AU  - Zeggini, E.
C1  - 56109
C2  - 46833
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S58-S59
TI  - Genome-wide analyses using uk biobank data povide new therapeutic targets for osteoarthritis.
JO  - Osteoarthr. Cartil.
VL  - 27
PB  - Elsevier Sci Ltd
PY  - 2019
SN  - 1063-4584
ER  - 

TY  - JOUR
AB  - OBJECTIVE: Considerable variation in total hip replacement and total knee replacement (THR/TKR) between regions has been described. The aim of this study was to explore geographical variation in THR and TKR in Germany and to analyse potentially explanatory variables. METHOD: We used data of Germany's largest statutory health insurer. Between 2005 and 2009 451,108 THR and 335,022 TKR were performed. Age-standardised joint replacement rates were calculated for 16 federal states and 407 counties. We performed cluster (Moran's I) and spatial error regression analyses including regional deprivation, osteoarthritis rate, urbanity and number of orthopaedic specialists as dependent variables on county level. RESULTS: In 2009 the overall age-standardised and crude rates were 148.9 (95% CI (confidence interval) 147.6-151.1) and 290.2 for THR, and 132.5 (95% CI 131.3-133.6) and 232.7 for TKR. Between counties THR rates differed by factor 2 (106.1-215.8) and showed significant clusters with high utilisation in South and Northwest Germany. TKR rates differed by factor 3.2 (69.1-219.5) and were also high in South Germany whereas almost all areas in East Germany showed low replacement rates. Differences were pronounced when restricting the analysis to cases with an indication of osteoarthritis. All tested predictors could be identified as significant explanatory variables (each P < 0.001). CONCLUSION: This study proofed considerable and consistent geographic variation of THR and TKR in Germany. Thereby relevant explanatory factors were identified. These results may foster the discussion and future research in health services which should include areas of patients' and doctors' expectation, financial aspects and an outcome-based definition of appropriate supply.
AU  - Schäfer, T.*
AU  - Pritzkuleit, R.*
AU  - Jeszenszky, C.*
AU  - Malzahn, J.*
AU  - Maier, W.
AU  - Günther, K.P.*
AU  - Niethard, F.*
C1  - 23115
C2  - 30997
SP  - 279-288
TI  - Trends and geographical variation of primary hip and knee joint replacement in Germany.
JO  - Osteoarthr. Cartil.
VL  - 21
IS  - 2
PB  - Elsevier
PY  - 2013
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - McWalter, E.J.*
AU  - Wirth, W.*
AU  - Siebert, M.
AU  - von Eisenhart-Rothe, R.*
AU  - Hudelmaier, M.*
AU  - Wilson, D.R.*
AU  - Eckstein, F.*
C1  - 5075
C2  - 22752
SP  - 48-53
TI  - Use of novel interactive input devices for segmentation of articular cartilage from magnetic resonance images.
JO  - Osteoarthr. Cartil.
VL  - 13
PY  - 2005
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Graichen, H.*
AU  - Jakob, J.*
AU  - von Eisenhart-Rothe, R.*
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
AU  - Eckstein, F.*
C1  - 22279
C2  - 21055
SP  - 475-482
TI  - Validation of cartilage volume and thickness measurements in the human shoulder with quantitative magnetic resonance imaging.
JO  - Osteoarthr. Cartil.
VL  - 11
PY  - 2003
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Eckstein, F.*
AU  - Müller, S.*
AU  - Faber, S.C.*
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
AU  - Putz, R.*
C1  - 9954
C2  - 20942
SP  - 914-921
TI  - Side differences of knee joint cartilage volume, thickness and surface area and correlation with lower limb dominance - an MRI-based study. 
JO  - Osteoarthr. Cartil.
VL  - 10
PY  - 2002
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Eckstein, F.*
AU  - Heudorfer, L.*
AU  - Faber, S.C.*
AU  - Burgkart, R.*
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
C1  - 9955
C2  - 20944
SP  - 922-928
TI  - Long-term and resegmentation precision of quantitative cartilage MR imaging (qMRI). 
JO  - Osteoarthr. Cartil.
VL  - 10
PY  - 2002
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Eckstein, F.*
AU  - Faber, S.*
AU  - Mühlbauer, R.*
AU  - Hohe, J.
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
AU  - Putz, R.*
C1  - 21998
C2  - 20532
SP  - 44-50
TI  - Functional adaption of human joints to mechanical stimuli.
JO  - Osteoarthr. Cartil.
VL  - 10
PY  - 2002
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Eckstein, F.*
AU  - Winzheimer, M.*
AU  - Hohe, J.*
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
C1  - 22172
C2  - 20872
SP  - 101-111
TI  - Interindividual variability and correlation among morphological parameters of knee joint cartilage plates : Analysis with three-dimensional MR imaging.
JO  - Osteoarthr. Cartil.
VL  - 9
PY  - 2001
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Graichen, H.*
AU  - Springer, V.*
AU  - Flaman, T.*
AU  - Stammberger, T.
AU  - Glaser, C.*
AU  - Englmeier, K.-H.
AU  - Reiser, M.*
AU  - Eckstein, F.*
C1  - 21529
C2  - 19650
SP  - 106-114
TI  - Validation of high-resolution water-excitation magnetic resonance imaging for quantitative assessment of thin cartilage layers.
JO  - Osteoarthr. Cartil.
VL  - 8
PY  - 2000
SN  - 1063-4584
ER  - 

TY  - JOUR
AU  - Hohe, J.
AU  - Faber, S.*
AU  - Stammberger, T.
AU  - Reiser, M.*
AU  - Englmeier, K.-H.
AU  - Eckstein, F.*
C1  - 21801
C2  - 19992
SP  - 426-433
TI  - A technique for 3D in vivo quantification of proton density and magnetization transfer coefficients of knee joint cartilage.
JO  - Osteoarthr. Cartil.
VL  - 8
PY  - 2000
SN  - 1063-4584
ER  -