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1,052 results on '"Kloppenburg, Margreet"'

2. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, Rosalie B. T. M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A. L. M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C. M., Linneberg, Allan, Lominchar, Jesus V. T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N. A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I. A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H. R., Wouters, Hanneke J. C. M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W. A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco

Published
2024
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9. Development and validation of a machine learning-supported strategy of patient selection for osteoarthritis clinical trials: the IMI-APPROACH study

Author

Widera, Paweł, Welsing, Paco M.J., Danso, Samuel O., Peelen, Sjaak, Kloppenburg, Margreet, Loef, Marieke, Marijnissen, Anne C., van Helvoort, Eefje M., Blanco, Francisco J., Magalhães, Joana, Berenbaum, Francis, Haugen, Ida K., Bay-Jensen, Anne-Christine, Mobasheri, Ali, Ladel, Christoph, Loughlin, John, Lafeber, Floris P.J.G., Lalande, Agnès, Larkin, Jonathan, Weinans, Harrie, and Bacardit, Jaume

Published
2023
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12. Colchicine twice a day for hand osteoarthritis (COLOR): a double-blind, randomised, placebo-controlled trial

Author

Døssing, Anna, Henriksen, Marius, Ellegaard, Karen, Nielsen, Sabrina Mai, Stamp, Lisa K, Müller, Felix C, Kloppenburg, Margreet, Haugen, Ida K, McCarthy, Geraldine M, Conaghan, Philip G, Ulff-Møller Dahl, Louise, Terslev, Lene, Altman, Roy D, Becce, Fabio, Ginnerup-Nielsen, Elisabeth, Jensen, Lene, Boesen, Mikael, Christensen, Robin, Dal, Ulla, and Bliddal, Henning

Published
2023
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13. Quantitative CT of the knee in the IMI-APPROACH osteoarthritis cohort: Association of bone mineral density with radiographic disease severity, meniscal coverage and meniscal extrusion

Author

Heiss, Rafael, Laredo, Jean-Denis, Wirth, Wolfgang, Jansen, Mylène P., Marijnissen, Anne C.A., Lafeber, Floris, Lalande, Agnes, Weinans, Harrie H., Blanco, Francisco J., Berenbaum, Francis, Kloppenburg, Margreet, Haugen, Ida K., Engelke, Klaus, and Roemer, Frank W.

Published
2023
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15. Serum Intestinal Permeability Biomarkers are associated with erosive hand osteoarthritis and radiographic severity: Results: from the DIGICOD cohort

Author

Binvignat, Marie, primary, Fellahi, Soraya, additional, Bastard, Jean-Philippe, additional, Rousseau, Alexandra, additional, Tuffet, Sophie, additional, Courties, Alice, additional, Pigenet, Audrey, additional, WANHERDRICK, Kristell, additional, Kloppenburg, Margreet, additional, Richette, Pascal, additional, Maheu, Emmanuel, additional, Crema, Michel D., additional, Klatzmann, David, additional, Sokol, Harry, additional, Mariotti-Ferrandiz, Encarnita, additional, Berenbaum, Francis, additional, and Sellam, Jeremie, additional

Published
2024
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16. Effects of Knee Flexion on Minimal Joint Space Width Increase in Knee Osteoarthritis Patients in the IMI-APPROACH cohort

Author

Bax, Eva, primary, Nguyen, Chien, additional, Custers, Roel J., additional, van Egmond, Nienke, additional, Arbabi, Vahid, additional, Rayegan, Hassan, additional, Paul Gielis, Willem, additional, Lindner, Claudia, additional, Cootes, Tim, additional, Kloppenburg, Margreet, additional, Blanco-Garcia, Francisco J, additional, Haugen, Ida K., additional, Berenbaum, Francis, additional, Jansen, Mylène P., additional, Mastbergen, Simon, additional, Wirth, Wolfgang, additional, Eckstein, Felix, additional, and Weinans, Harrie, additional

Published
2024
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22. Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort

Author

Roemer, Frank W., Jansen, Mylène, Marijnissen, Anne C. A., Guermazi, Ali, Heiss, Rafael, Maschek, Susanne, Lalande, Agnes, Blanco, Francisco J., Berenbaum, Francis, van de Stadt, Lotte A., Kloppenburg, Margreet, Haugen, Ida K., Ladel, Christoph H., Bacardit, Jaume, Wisser, Anna, Eckstein, Felix, Lafeber, Floris P. J. G., Weinans, Harrie H., and Wirth, Wolfgang

Published
2022
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24. DIGICOD, cohorte prospective observationnelle hospitalière de patients souffrant d’arthrose digitale : méthodologie et caractéristiques de la population d’inclusion

Author

Sellam, Jérémie, Maheu, Emmanuel, Crema, Michel D., Touati, Amel, Courties, Alice, Tuffet, Sophie, Rousseau, Alexandra, Chevalier, Xavier, Combe, Bernard, Dougados, Maxime, Fautrel, Bruno, Kloppenburg, Margreet, Laredo, Jean-Denis, Loeuille, Damien, Miquel, Anne, Rannou, François, Richette, Pascal, Simon, Tabassome, and Berenbaum, Francis

Published
2022
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25. A Damaging COL6A3 Variant Alters the MIR31HG‐Regulated Response of Chondrocytes in Neocartilage Organoids to Hyperphysiologic Mechanical Loading.

Author

Bloks, Niek GC, Harissa, Zainab, Mazzini, Giorgia, Adkar, Shaunak S, Dicks, Amanda R, Hajmousa, Ghazaleh, Steward, Nancy, Koning, Roman I., Mulder, Aat, de Koning, Berend B.R., Kloppenburg, Margreet, de Almeida, Rodrigo Coutinho, Ramos, Yolande FM, Guilak, Farshid, and Meulenbelt, Ingrid

Subjects
GENOME editing, CYCLOOXYGENASE 2, GENETIC variation, INFLAMMATION, CARTILAGE cells
Abstract

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR‐Cas9 genome engineering in two established human induced pluripotent stem cell‐derived in‐vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi‐omics (mRNA and lncRNA) approach in interaction with hyper‐physiological mechanical loading conditions. The damaging variant in COL6A3 results in significantly lower binding between the PCM proteins COLVI and FN and provokes an osteoarthritic chondrocyte state. By subsequently exposing the neocartilage organoids to hyperphysiological mechanical stress, it is demonstrated that the COL6A3 variant in chondrocytes abolishes the characteristic inflammatory signaling response after mechanical loading with PTGS2, PECAM1, and ADAMTS5, as central genes. Finally, by integrating epigenetic regulation, the lncRNA MIR31HG is identified as key regulator of the characteristic inflammatory signaling response to mechanical loading. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Atlas for the OMERACT thumb base osteoarthritis MRI scoring system (TOMS)

Author

Kroon, Féline PB, Peterfy, Charles G, Conaghan, Philip G, Foltz, Violaine, Gandjbakhch, Frédérique, Eshed, Iris, Genant, Harry K, Østergaard, Mikkel, Reijnierse, Monique, Bloem, Johan L, Haugen, Ida K, and Kloppenburg, Margreet

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Arthritis, Aging, Osteoarthritis, Musculoskeletal, hand osteoarthritis, magnetic resonance imaging, osteoarthritis, Clinical sciences
Abstract

This paper presents an atlas for the Outcome Measures in Rheumatology Clinical Trials (OMERACT) thumb base osteoarthritis MRI scoring system (TOMS). The atlas includes reference images of each grade of each feature that is assessed in TOMS (synovitis grade 0-3, subchondral bone defects grade 0-3, osteophytes grade 0-3, cartilage assessment grade 0-3, subluxation and bone marrow lesions grade 0-3) in the first carpometacarpal and scapho-trapezio-trapezoid joint. The presented reference images can be used to guide scoring of thumb base MRIs in patients with hand osteoarthritis according to the OMERACT TOMS.

Published
2018

31. The DIGICOD cohort: A hospital-based observational prospective cohort of patients with hand osteoarthritis – methodology and baseline characteristics of the population

Author

Sellam, Jérémie, Maheu, Emmanuel, Crema, Michel D., Touati, Amel, Courties, Alice, Tuffet, Sophie, Rousseau, Alexandra, Chevalier, Xavier, Combe, Bernard, Dougados, Maxime, Fautrel, Bruno, Kloppenburg, Margreet, Laredo, Jean-Denis, Loeuille, Damien, Miquel, Anne, Rannou, François, Richette, Pascal, Simon, Tabassome, and Berenbaum, Francis

Published
2021
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32. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, Medici, Marco, Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco

Abstract

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

33. Evaluation of the Diagnostic Performance of American College of Rheumatology, EULAR, and National Institute for Health and Clinical Excellence Criteria Against Clinically Relevant Knee Osteoarthritis:Data From the CHECK Cohort

Author

Wang, Qiuke, Runhaar, Jos, Kloppenburg, Margreet, Boers, Maarten, Bijlsma, Johannes W. J., Bierma-Zeinstra, Sita M. A., Wang, Qiuke, Runhaar, Jos, Kloppenburg, Margreet, Boers, Maarten, Bijlsma, Johannes W. J., and Bierma-Zeinstra, Sita M. A.

Abstract

ObjectiveOur objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by using clinical experts' diagnosis of clinically relevant knee osteoarthritis (OA) as the outcome of interest.MethodsIn a previous study, we recruited clinical experts to evaluate longitudinal (5-, 8-, and 10-year follow-up) clinical and radiographic data of symptomatic knees from the Cohort Hip and Cohort Knee (CHECK) study for the presence or absence of clinically relevant OA. In the current study, ACR, EULAR, and NICE criteria were applied to the same 5-, 8-, and 10-year follow-up data; then a knee was diagnosed with OA if fulfilling the criteria at one of the three time points (F1), two of the time points (F2), or at all three time points (F3). Using clinically relevant OA as the reference standard, the sensitivity, specificity, and positive and negative predictive values for the three criteria were assessed.ResultsA total of 539 participants for a total of 833 examined knees were included. Thirty-six percent of knees were diagnosed with clinically relevant OA by experts. Sixty-seven percent to 74% of the knees received the same diagnosis (OA or non-OA) by the three criteria sets for the different definitions (F1 to F3). EULAR consistently (F1 through F3) had the highest specificity, and NICE consistently had the highest sensitivity.ConclusionThe diagnoses only moderately overlapped among the three criteria sets. The EULAR criteria seemed to be more suitable for study enrollment (when aimed at recruiting clinically relevant OA knees), given the highest specificities. The NICE criteria, given the highest sensitivities, could be more useful for an initial diagnosis in clinical practice.

Published
2024

34. Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis?: data from the IMI-APPROACH cohort

Author

Jansen, Mylène P., Hodgins, Diana, Mastbergen, Simon C., Kloppenburg, Margreet, Blanco García, Francisco J, Haugen, Ida K., Berenbaum, Francis, Eckstein, Felix, Roemer, Frank W., Wirt, Wolfgang, Jansen, Mylène P., Hodgins, Diana, Mastbergen, Simon C., Kloppenburg, Margreet, Blanco García, Francisco J, Haugen, Ida K., Berenbaum, Francis, Eckstein, Felix, Roemer, Frank W., and Wirt, Wolfgang

Abstract

[Abstract] Objective: To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). Methods: IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. Results: Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identified two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically significantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2 = 0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed significantly worse lower leg gait (R2 = 0.18). Higher BMI was significantly associated with reduced upper leg function for non-ROA patients (R2 = 0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed significantly worse upper leg gait (R2 = 0.12). Conclusion: Structural OA pathology was significantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a significant association between OA symptoms (gait) and joint structure.

Published
2024

35. Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.

Author

Castaño-Betancourt, Martha C, Evans, Dan S, Ramos, Yolande FM, Boer, Cindy G, Metrustry, Sarah, Liu, Youfang, den Hollander, Wouter, van Rooij, Jeroen, Kraus, Virginia B, Yau, Michelle S, Mitchell, Braxton D, Muir, Kenneth, Hofman, Albert, Doherty, Michael, Doherty, Sally, Zhang, Weiya, Kraaij, Robert, Rivadeneira, Fernando, Barrett-Connor, Elizabeth, Maciewicz, Rose A, Arden, Nigel, Nelissen, Rob GHH, Kloppenburg, Margreet, Jordan, Joanne M, Nevitt, Michael C, Slagboom, Eline P, Hart, Deborah J, Lafeber, Floris, Styrkarsdottir, Unnur, Zeggini, Eleftheria, Evangelou, Evangelos, Spector, Tim D, Uitterlinden, Andre G, Lane, Nancy E, Meulenbelt, Ingrid, Valdes, Ana M, and van Meurs, Joyce BJ

Subjects
Cartilage, Hip Joint, Humans, Osteoarthritis, Hip, Genetic Predisposition to Disease, Trehalase, Transforming Growth Factor alpha, Regulatory Sequences, Nucleic Acid, Genetic Heterogeneity, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Receptor, Fibroblast Growth Factor, Type 3, Genome-Wide Association Study, Phosphatidylinositol 3-Kinases, Class Ia Phosphatidylinositol 3-Kinase, Osteoarthritis, Hip, Regulatory Sequences, Nucleic Acid, Polymorphism, Single Nucleotide, and over, Receptor, Fibroblast Growth Factor, Type 3, Genetics, Developmental Biology
Abstract

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies.

Published
2016

37. The transcriptional landscape of age in human peripheral blood.

Author

Peters, Marjolein J, Joehanes, Roby, Pilling, Luke C, Schurmann, Claudia, Conneely, Karen N, Powell, Joseph, Reinmaa, Eva, Sutphin, George L, Zhernakova, Alexandra, Schramm, Katharina, Wilson, Yana A, Kobes, Sayuko, Tukiainen, Taru, NABEC/UKBEC Consortium, Ramos, Yolande F, Göring, Harald HH, Fornage, Myriam, Liu, Yongmei, Gharib, Sina A, Stranger, Barbara E, De Jager, Philip L, Aviv, Abraham, Levy, Daniel, Murabito, Joanne M, Munson, Peter J, Huan, Tianxiao, Hofman, Albert, Uitterlinden, André G, Rivadeneira, Fernando, van Rooij, Jeroen, Stolk, Lisette, Broer, Linda, Verbiest, Michael MPJ, Jhamai, Mila, Arp, Pascal, Metspalu, Andres, Tserel, Liina, Milani, Lili, Samani, Nilesh J, Peterson, Pärt, Kasela, Silva, Codd, Veryan, Peters, Annette, Ward-Caviness, Cavin K, Herder, Christian, Waldenberger, Melanie, Roden, Michael, Singmann, Paula, Zeilinger, Sonja, Illig, Thomas, Homuth, Georg, Grabe, Hans-Jörgen, Völzke, Henry, Steil, Leif, Kocher, Thomas, Murray, Anna, Melzer, David, Yaghootkar, Hanieh, Bandinelli, Stefania, Moses, Eric K, Kent, Jack W, Curran, Joanne E, Johnson, Matthew P, Williams-Blangero, Sarah, Westra, Harm-Jan, McRae, Allan F, Smith, Jennifer A, Kardia, Sharon LR, Hovatta, Iiris, Perola, Markus, Ripatti, Samuli, Salomaa, Veikko, Henders, Anjali K, Martin, Nicholas G, Smith, Alicia K, Mehta, Divya, Binder, Elisabeth B, Nylocks, K Maria, Kennedy, Elizabeth M, Klengel, Torsten, Ding, Jingzhong, Suchy-Dicey, Astrid M, Enquobahrie, Daniel A, Brody, Jennifer, Rotter, Jerome I, Chen, Yii-Der I, Houwing-Duistermaat, Jeanine, Kloppenburg, Margreet, Slagboom, P Eline, Helmer, Quinta, den Hollander, Wouter, Bean, Shannon, Raj, Towfique, Bakhshi, Noman, Wang, Qiao Ping, Oyston, Lisa J, Psaty, Bruce M, Tracy, Russell P, Montgomery, Grant W, and Turner, Stephen T

Subjects
NABEC/UKBEC Consortium, Humans, Gene Expression Profiling, DNA Methylation, Aging, European Continental Ancestry Group, Transcriptome, Biomarkers
Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Published
2015

38. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

Author

Evangelou, Evangelos, Kerkhof, Hanneke J, Styrkarsdottir, Unnur, Ntzani, Evangelia E, Bos, Steffan D, Esko, Tonu, Evans, Daniel S, Metrustry, Sarah, Panoutsopoulou, Kalliope, Ramos, Yolande FM, Thorleifsson, Gudmar, Tsilidis, Konstantinos K, Consortium, arcOGEN, Arden, Nigel, Aslam, Nadim, Bellamy, Nicholas, Birrell, Fraser, Blanco, Francisco J, Carr, Andrew, Chapman, Kay, Day-Williams, Aaron G, Deloukas, Panos, Doherty, Michael, Engström, Gunnar, Helgadottir, Hafdis T, Hofman, Albert, Ingvarsson, Thorvaldur, Jonsson, Helgi, Keis, Aime, Keurentjes, J Christiaan, Kloppenburg, Margreet, Lind, Penelope A, McCaskie, Andrew, Martin, Nicholas G, Milani, Lili, Montgomery, Grant W, Nelissen, Rob GHH, Nevitt, Michael C, Nilsson, Peter M, Ollier, William ER, Parimi, Neeta, Rai, Ashok, Ralston, Stuart H, Reed, Mike R, Riancho, Jose A, Rivadeneira, Fernando, Rodriguez-Fontenla, Cristina, Southam, Lorraine, Thorsteinsdottir, Unnur, Tsezou, Aspasia, Wallis, Gillian A, Wilkinson, J Mark, Gonzalez, Antonio, Lane, Nancy E, Lohmander, L Stefan, Loughlin, John, Metspalu, Andres, Uitterlinden, Andre G, Jonsdottir, Ingileif, Stefansson, Kari, Slagboom, P Eline, Zeggini, Eleftheria, Meulenbelt, Ingrid, Ioannidis, John PA, Spector, Tim D, van Meurs, Joyce BJ, and Valdes, Ana M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Prevention, Osteoarthritis, Human Genome, Arthritis, Genetics, Aging, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, HMGN Proteins, Homeodomain Proteins, Humans, Immediate-Early Proteins, Male, Nuclear Receptor Coactivator 3, Osteoarthritis, Hip, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Protein-Tyrosine Kinases, Sex Factors, White People, arcOGEN Consortium, Epidemiology, Gene Polymorphism, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectivesOsteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.MethodsWe performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used.ResultsWe accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis).ConclusionsNovel genetic loci for hip OA were found in this meta-analysis of GWAS.

Published
2014

42. Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2023.

Author

Winthrop, Kevin L., Mease, Philip, Kerschbaumer, Andreas, Voll, Reinhard E., Breedveld, Ferdinand C., Smolen, Josef S., Gottenberg, Jacques-Eric, Baraliakos, Xenofon, Kiener, Hans P., Aletaha, Daniel, Isaacs, John D., Buch, Maya H., Crow, Mary K., Kay, Jonathan, Crofford, Leslie, van Vollenhoven, Ronald F., Ospelt, Caroline, Siebert, Stefan, Kloppenburg, Margreet, and McInnes, Iain B.

Published
2024
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46. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author

Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John RB, Yuan, Xin, Scott, Robert A, Henneman, Peter, Heid, Iris M, Kizer, Jorge R, Lyytikäinen, Leo-Pekka, Fuchsberger, Christian, Tanaka, Toshiko, Morris, Andrew P, Small, Kerrin, Isaacs, Aaron, Beekman, Marian, Coassin, Stefan, Lohman, Kurt, Qi, Lu, Kanoni, Stavroula, Pankow, James S, Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J, Greenwood, Celia MT, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Liu, Ching-Ti, Kooner, Jaspal, Mooser, Vincent E, Vollenweider, Peter, Kapur, Karen A, Chambers, John, Wareham, Nicholas J, Langenberg, Claudia, Frants, Rune, Willems-Vandijk, Ko, Oostra, Ben A, Willems, Sara M, Lamina, Claudia, Winkler, Thomas W, Psaty, Bruce M, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P, Evans, David M, St Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, van Heemst, Diana, Kedenko, Lyudmyla, Kristiansson, Kati, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Garcia, Melissa, Kanaya, Alka, Haun, Margot, Klopp, Norman, Wichmann, H-Erich, Deloukas, Panos, Katsareli, Efi, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Adair, Linda S, Borja, Judith B, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson, James G, Musani, Solomon, Guo, Xiuqing, Johnson, Toby, Semple, Robert, Teslovich, Tanya M, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Hu, Frank B, Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D, Slagboom, P Eline, Ferrucci, Luigi, and Jula, Antti

Subjects
DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Humans, Diabetes Mellitus, Type 2, Insulin Resistance, Genetic Predisposition to Disease, Glucose Tolerance Test, Waist-Hip Ratio, Gene Expression, Polymorphism, Single Nucleotide, African Americans, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiponectin, Cholesterol, HDL, Metabolic Networks and Pathways, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Cholesterol, HDL, Genetics, Developmental Biology
Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Published
2012

47. Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis

Author

Kerkhof, Hanneke JM, Meulenbelt, Ingrid, Carr, Andrew, Gonzalez, Antonio, Hart, Deborah, Hofman, Albert, Kloppenburg, Margreet, Lane, Nancy E, Loughlin, John, Nevitt, Michael C, Pols, Huibert AP, Rivadeneira, Fernando, Slagboom, Eline P, Spector, Tim D, Stolk, Lisette, Tsezou, Aspasia, Uitterlinden, André G, Valdes, Ana M, and van Meurs, Joyce BJ

Abstract

Abstract Background The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis. Methods In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls. Results The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05). Conclusion This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.

Published
2010

48. Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials

Author

Døssing, Anna, primary, Nielsen, Sabrina Mai, additional, Kroon, Féline PB, additional, Balsby, Ida Maria, additional, Tarp, Simon, additional, Kloppenburg, Margreet, additional, Stamp, Lisa, additional, Haugen, Ida K, additional, Altman, Roy D, additional, Henriksen, Marius, additional, Boesen, Mikael, additional, Bliddal, Henning, additional, Berg, Søren, additional, and Christensen, Robin, additional

Published
2023
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50. Improvement of Pain Symptoms in Musculoskeletal Diseases After Multimodal Spa Therapy in the Austrian Gastein Valley—A Study Based on Longitudinal Registry Data

Author

van der Zee-Neuen, Antje, primary, Fuchs, Julia, additional, Wildburger, Sonja, additional, Gaisberger, Martin, additional, Kloppenburg, Margreet, additional, Fioravanti, Antonella, additional, Stamm, Tanja, additional, Offenbaecher, Martin, additional, Radlmueller, Rudolf, additional, Foisner, Wolfgang, additional, Hoelzl, Bertram, additional, and Ritter, Markus, additional

Published
2023
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