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3. 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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4. Multi-classifier prediction of knee osteoarthritis progression from incomplete imbalanced longitudinal data

Author

Widera, Paweł, Welsing, Paco M. J., Ladel, Christoph, Loughlin, John, Lafeber, Floris P. J. G., Dop, Florence Petit, Larkin, Jonathan, Weinans, Harrie, Mobasheri, Ali, and Bacardit, Jaume

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Conventional inclusion criteria used in osteoarthritis clinical trials are not very effective in selecting patients who would benefit from a therapy being tested. Typically majority of selected patients show no or limited disease progression during a trial period. As a consequence, the effect of the tested treatment cannot be observed, and the efforts and resources invested in running the trial are not rewarded. This could be avoided, if selection criteria were more predictive of the future disease progression. In this article, we formulated the patient selection problem as a multi-class classification task, with classes based on clinically relevant measures of progression (over a time scale typical for clinical trials). Using data from two long-term knee osteoarthritis studies OAI and CHECK, we tested multiple algorithms and learning process configurations (including multi-classifier approaches, cost-sensitive learning, and feature selection), to identify the best performing machine learning models. We examined the behaviour of the best models, with respect to prediction errors and the impact of used features, to confirm their clinical relevance. We found that the model-based selection outperforms the conventional inclusion criteria, reducing by 20-25% the number of patients who show no progression. This result might lead to more efficient clinical trials., Comment: 22 pages, 12 figures, 10 tables

Published
2019
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5. Initial direct cost and deferred rent under FASB ASC 842: Topic 842 requires that initial direct costs be added to the right-of-use asset and included in its subsequent amortization

Author

Singer, Robert, Bosnick, James, Hays, Bailey, and Loughlin, John

Subjects
Deferred income (Business) -- Laws, regulations and rules -- Taxation, Leases -- Laws, regulations and rules -- Taxation, Government regulation, Banking, finance and accounting industries, Business, Law
Abstract

FASB Accounting Standards Codification (ASC) Topic 842, Leases, issued in February 2016, marked a significant overhaul in the financial reporting of long-term leases. Its adoption created many challenges for public [...]

Published
2023

6. Research priorities to reduce the impact of musculoskeletal disorders: a priority setting exercise with the child health and nutrition research initiative method

Author

Paskins, Zoe, Farmer, Clare E, Manning, Fay, Andersson, David A, Barlow, Tim, Bishop, Felicity L, Brown, Christopher A, Clark, Amanda, Clark, Emma M, Dulake, Debra, Gulati, Malvika, Le Maitre, Christine L, Jones, Richard K, Loughlin, John, Mason, Deborah J, McCarron, Maura, Millar, Neil L, Pandit, Hemant, Peat, George, Richardson, Stephen M, Salt, Emma J, Taylor, E Jane, Troeberg, Linda, Wilcox, Ruth K, Wise, Elspeth, Wilkinson, Colin, and Watt, Fiona E

Published
2022
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13. 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

22. 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

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

Author

MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Lab Reumatologie/Klinische Immunologie, ORT Research, 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, Bacardit, Jaume, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, Lab Reumatologie/Klinische Immunologie, ORT Research, 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

31. Predicted and actual 2-year structural and pain progression in the IMI-APPROACH knee osteoarthritis cohort

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Regenerative Medicine and Stem Cells, ORT Research, JC onderzoeksprogramma Methodologie, van Helvoort, Eefje M, Jansen, Mylène P, Marijnissen, Anne C A, Kloppenburg, Margreet, Blanco, Francisco J, Haugen, Ida K, Berenbaum, Francis, Bay-Jensen, Anne-Christine C, Ladel, Christoph, Lalande, Agnes, Larkin, Jonathan, Loughlin, John, Mobasheri, Ali, Weinans, Harrie H, Widera, Pawel, Bacardit, Jaume, Welsing, Paco M J, Lafeber, Floris P J G, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Regenerative Medicine and Stem Cells, ORT Research, JC onderzoeksprogramma Methodologie, van Helvoort, Eefje M, Jansen, Mylène P, Marijnissen, Anne C A, Kloppenburg, Margreet, Blanco, Francisco J, Haugen, Ida K, Berenbaum, Francis, Bay-Jensen, Anne-Christine C, Ladel, Christoph, Lalande, Agnes, Larkin, Jonathan, Loughlin, John, Mobasheri, Ali, Weinans, Harrie H, Widera, Pawel, Bacardit, Jaume, Welsing, Paco M J, and Lafeber, Floris P J G

Published
2023

45. Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Styrkarsdottir, Unnur, Stefansson, Olafur A., Gunnarsdottir, Kristbjorg, Thorleifsson, Gudmar, Lund, Sigrun H., Stefansdottir, Lilja, Juliusson, Kristinn, Agustsdottir, Arna B., Zink, Florian, Halldorsson, Gisli H., Ivarsdottir, Erna V., Benonisdottir, Stefania, Jonsson, Hakon, Gylfason, Arnaldur, Norland, Kristjan, Trajanoska, Katerina, Boer, Cindy G., Southam, Lorraine, Leung, Jason C. S., Tang, Nelson L. S., Kwok, Timothy C. Y., Lee, Jenny S. W., Ho, Suzanne C., Byrjalsen, Inger, Center, Jacqueline R., Lee, Seung Hun, Koh, Jung-Min, Lohmander, L. Stefan, Ho-Pham, Lan T., Nguyen, Tuan V., Eisman, John A., Woo, Jean, Leung, Ping-C., Loughlin, John, Zeggini, Eleftheria, Christiansen, Claus, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, Andre G., Mogensen, Brynjolfur, Jonsson, Helgi, Ingvarsson, Thorvaldur, Sigurdsson, Gunnar, Benediktsson, Rafn, Sulem, Patrick, Jonsdottir, Ingileif, Masson, Gisli, Holm, Hilma, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2019
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46. GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Styrkarsdottir, Unnur, Stefansson, Olafur A., Gunnarsdottir, Kristbjorg, Thorleifsson, Gudmar, Lund, Sigrun H., Stefansdottir, Lilja, Juliusson, Kristinn, Agustsdottir, Arna B., Zink, Florian, Halldorsson, Gisli H., Ivarsdottir, Erna V., Benonisdottir, Stefania, Jonsson, Hakon, Gylfason, Arnaldur, Norland, Kristjan, Trajanoska, Katerina, Boer, Cindy G., Southam, Lorraine, Leung, Jason C. S., Tang, Nelson L. S., Kwok, Timothy C. Y., Lee, Jenny S. W., Ho, Suzanne C., Byrjalsen, Inger, Center, Jacqueline R., Lee, Seung Hun, Koh, Jung-Min, Lohmander, L. Stefan, Ho-Pham, Lan T., Nguyen, Tuan V., Eisman, John A., Woo, Jean, Leung, Ping-C., Loughlin, John, Zeggini, Eleftheria, Christiansen, Claus, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, Andre G., Mogensen, Brynjolfur, Jonsson, Helgi, Ingvarsson, Thorvaldur, Sigurdsson, Gunnar, Benediktsson, Rafn, Sulem, Patrick, Jonsdottir, Ingileif, Masson, Gisli, Holm, Hilma, Norddahl, Gudmundur L., Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2019
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47. Additional file 10 of Osteoarthritis genetic risk acting on the galactosyltransferase gene COLGALT2 has opposing functional effects in articulating joint tissues

Author

Kehayova, Yulia S., Wilkinson, J. Mark, Rice, Sarah J., and Loughlin, John

Abstract

Additional file 10. Flow version of Fig. 7. (A) The causal variant has hypothetical alleles C (risk) and T (non-risk). (B) In synovium, these alleles differentially bind transcription factors TF1 and TF2; in cartilage, they differentially bind transcription factors TF3 and TF4. (C) Differential transcription factor binding at the variant leads to allele-specific methylation of the enhancer. (D) This results in quantitative differences in the binding of a common transcription factor (TF5) at the enhancer. (E) Low levels of bound TF5 lead to low levels of COLGALT2 transcription. In synovium, risk allele C is more methylated at the enhancer than non-risk allele T, resulting in less TF5 binding to, and therefore relatively low transcription of, allele C. The opposite is the case in cartilage. The model predicts that for both tissues, decreased enhancer methylation increases COLGALT2 expression, and vice versa.

Published
2023
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48. Additional file 4 of Osteoarthritis genetic risk acting on the galactosyltransferase gene COLGALT2 has opposing functional effects in articulating joint tissues

Author

Kehayova, Yulia S., Wilkinson, J. Mark, Rice, Sarah J., and Loughlin, John

Abstract

Additional file 4. Age versus methylation. Linear regression was used to test for association between age at surgery inyears and DNA methylation levels at cg18131582 (CpG9) and its 11 flanking CpGs. DNAm, DNA methylation. Each dot is data from one individual.

Published
2023
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