Search

Your search keyword '"König, Inke R."' showing total 1,174 results
Start Over Author "König, Inke R."
1,174 results on '"König, Inke R."'

3. Effect of hyperparameters on variable selection in random forests

Author

Fouodo, Cesaire J. K., Kronziel, Lea L., König, Inke R., and Szymczak, Silke

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

Random forests (RFs) are well suited for prediction modeling and variable selection in high-dimensional omics studies. The effect of hyperparameters of the RF algorithm on prediction performance and variable importance estimation have previously been investigated. However, how hyperparameters impact RF-based variable selection remains unclear. We evaluate the effects on the Vita and the Boruta variable selection procedures based on two simulation studies utilizing theoretical distributions and empirical gene expression data. We assess the ability of the procedures to select important variables (sensitivity) while controlling the false discovery rate (FDR). Our results show that the proportion of splitting candidate variables (mtry.prop) and the sample fraction (sample.fraction) for the training dataset influence the selection procedures more than the drawing strategy of the training datasets and the minimal terminal node size. A suitable setting of the RF hyperparameters depends on the correlation structure in the data. For weakly correlated predictor variables, the default value of mtry is optimal, but smaller values of sample.fraction result in larger sensitivity. In contrast, the difference in sensitivity of the optimal compared to the default value of sample.fraction is negligible for strongly correlated predictor variables, whereas smaller values than the default are better in the other settings. In conclusion, the default values of the hyperparameters will not always be suitable for identifying important variables. Thus, adequate values differ depending on whether the aim of the study is optimizing prediction performance or variable selection., Comment: 18 pages, 2 figures + 2 figures in appendix, 3 tables

Published
2023

6. Effects of a rater training on rating accuracy in a physical examination skills assessment

Author

Weitz, Gunther, Vinzentius, Christian, Twesten, Christoph, Lehnert, Hendrik, Bonnemeier, Hendrik, and König, Inke R.

Subjects
rater training, rating accuracy, skills assessment, physical examination skills, randomised controlled trial, Special aspects of education, LC8-6691, Medicine (General), R5-920
Abstract

[english] Background: The accuracy and reproducibility of medical skills assessment is generally low. Rater training has little or no effect. Our knowledge in this field, however, relies on studies involving video ratings of overall clinical performances. We hypothesised that a rater training focussing on the frame of reference could improve accuracy in grading the curricular assessment of a highly standardised physical head-to-toe examination.Methods: Twenty-one raters assessed the performance of 242 third-year medical students. Eleven raters had been randomly assigned to undergo a brief frame-of-reference training a few days before the assessment. 218 encounters were successfully recorded on video and re-assessed independently by three additional observers. Accuracy was defined as the concordance between the raters' grade and the median of the observers' grade. After the assessment, both students and raters filled in a questionnaire about their views on the assessment.Results: Rater training did not have a measurable influence on accuracy. However, trained raters rated significantly more stringently than untrained raters, and their overall stringency was closer to the stringency of the observers. The questionnaire indicated a higher awareness of the halo effect in the trained raters group. Although the self-assessment of the students mirrored the assessment of the raters in both groups, the students assessed by trained raters felt more discontent with their grade.Conclusions: While training had some marginal effects, it failed to have an impact on the individual accuracy. These results in real-life encounters are consistent with previous studies on rater training using video assessments of clinical performances. The high degree of standardisation in this study was not suitable to harmonize the trained raters’ grading. The data support the notion that the process of appraising medical performance is highly individual. A frame-of-reference training as applied does not effectively adjust the physicians' judgement on medical students in real-live assessments.

Published
2014
Full Text
View/download PDF

11. An incremental procedure model for e-learning projects at universities

Author

Pahlke, Friedrich, König, Inke R., Bischoff, Michael, and Ziegler, Andreas

Subjects
E-learning, didactical concept, instructional design, procedure model, Genetic Epidemiology, Computer applications to medicine. Medical informatics, R858-859.7, Infectious and parasitic diseases, RC109-216
Abstract

E-learning projects at universities are produced under different conditions than in industry. The main characteristic of many university projects is that these are realized quasi in a solo effort. In contrast, in private industry the different, interdisciplinary skills that are necessary for the development of e-learning are typically supplied by a multimedia agency.A specific procedure tailored for the use at universities is therefore required to facilitate mastering the amount and complexity of the tasks.In this paper an incremental procedure model is presented, which describes the proceeding in every phase of the project. It allows a high degree of flexibility and emphasizes the didactical concept – instead of the technical implementation. In the second part, we illustrate the practical use of the theoretical procedure model based on the project “Online training in Genetic Epidemiology”.

Published
2006

12. Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial

Author

Krug, David, Zaman, Adrian, Eidinger, Lina, Grehn, Melanie, Boda-Heggemann, Judit, Rudic, Boris, Mehrhof, Felix, Boldt, Leif-Hendrik, Hohmann, Stephan, Merten, Roland, Buergy, Daniel, Fleckenstein, Jens, Kluge, Anne, Rogge, Annette, Both, Marcus, Rades, Dirk, Tilz, Roland Richard, Olbrich, Denise, König, Inke R., Siebert, Frank-Andre, Schweikard, Achim, Vonthein, Reinhard, Bonnemeier, Hendrik, Dunst, Jürgen, and Blanck, Oliver

Published
2023
Full Text
View/download PDF

16. Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19: Results of a retrospective multicenter neuroimaging-based study from three central European countries

Author

Jensen-Kondering, Ulf, Maurer, Christoph J., Brudermann, Hanna C. B., Ernst, Marielle, Sedaghat, Sam, Margraf, Nils G., Bahmer, Thomas, Jansen, Olav, Nawabi, Jawed, Vogt, Estelle, Büttner, Laura, Siebert, Eberhard, Bartl, Michael, Maus, Volker, Werding, Gregor, Schlamann, Marc, Abdullayev, Nuran, Bender, Benjamin, Richter, Vivien, Mengel, Annerose, Göpel, Siri, Berlis, Ansgar, Grams, Astrid, Ladenhauf, Valentin, Gizewski, Elke R., Kindl, Philipp, Schulze-Zachau, Victor, Psychogios, Marios, König, Inke R., Sondermann, Stefan, Wallis, Sönke, Brüggemann, Norbert, Schramm, Peter, and Neumann, Alexander

Published
2023
Full Text
View/download PDF

18. Empowering individual trait prediction using interactions

Author

Gola, Damian and König, Inke R.

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

One component of precision medicine is to construct prediction models with their predictive ability as high as possible, e.g. to enable individual risk prediction. In genetic epidemiology, complex diseases have a polygenic basis and a common assumption is that biological and genetic features affect the outcome under consideration via interactions. In the case of omics data, the use of standard approaches such as generalized linear models may be suboptimal and machine learning methods are appealing to make individual predictions. However, most of these algorithms focus mostly on main or marginal effects of the single features in a dataset. On the other hand, the detection of interacting features is an active area of research in the realm of genetic epidemiology. One big class of algorithms to detect interacting features is based on the multifactor dimensionality reduction (MDR). Here, we extend the model-based MDR (MB-MDR), a powerful extension of the original MDR algorithm, to enable interaction empowered individual prediction. Using a comprehensive simulation study we show that our new algorithm can use information hidden in interactions more efficiently than two other state-of-the-art algorithms, namely the Random Forest and Elastic Net, and clearly outperforms these if interactions are present. The performance of these algorithms is comparable if no interactions are present. Further, we show that our new algorithm is applicable to real data by comparing the performance of the three algorithms on a dataset of rheumatoid arthritis cases and healthy controls. As our new algorithm is not only applicable to biological/genetic data but to all datasets with discrete features, it may have practical implications in other applications as well, and we made our method available as an R package., Comment: 35 pages, 5 figures

Published
2019

23. Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke

Author

Schweizer, Juliane, Arnold, Markus, König, Inke R., Bicvic, Antonela, Westphal, Laura P., Schütz, Valerie, Inauen, Corinne, Scherrer, Natalie, Luft, Andreas, Galovic, Marian, Ferreira Atuesta, Carolina, Pokorny, Thomas, Arnold, Marcel, Fischer, Urs, Bonati, Leo H., De Marchis, Gian Marco, Kahles, Timo, Nedeltchev, Krassen, Cereda, Carlo W., Kägi, Georg, Bustamante, Alejandro, Montaner, Joan, Ntaios, Georg, Sagris, Dimitrios, Foerch, Christian, Spanaus, Katharina, von Eckardstein, Arnold, and Katan, Mira

Published
2022
Full Text
View/download PDF

24. Stability of Mosaic Divergent Repeat Interruptions in X‐Linked Dystonia‐Parkinsonism

Author

Laß, Joshua, primary, Lüth, Theresa, additional, Schlüter, Kathleen, additional, Schaake, Susen, additional, Laabs, Björn‐Hergen, additional, Much, Christoph, additional, Jamora, Roland Dominic, additional, Rosales, Raymond L., additional, Saranza, Gerard, additional, Diesta, Cid Czarina E., additional, Pearson, Christopher E., additional, König, Inke R., additional, Brüggemann, Norbert, additional, Klein, Christine, additional, Westenberger, Ana, additional, and Trinh, Joanne, additional

Published
2024
Full Text
View/download PDF

25. Impact of guideline changes on adoption of hypofractionation and breast cancer patient characteristics in the randomized controlled HYPOSIB trial

Author

Krug, David, Vonthein, Reinhard, Schreiber, Andreas, Boicev, Alexander D., Zimmer, Jörg, Laubach, Reinhold, Weidner, Nicola, Dinges, Stefan, Hipp, Matthias, Schneider, Ralf, Weinstrauch, Evelyn, Martin, Thomas, Hörner-Rieber, Juliane, Olbrich, Denise, Illen, Alicia, Heßler, Nicole, König, Inke R., Dellas, Kathrin, and Dunst, Jürgen

Published
2021
Full Text
View/download PDF

26. Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement

Author

Feistritzer, Hans-Josef, Kurz, Thomas, Stachel, Georg, Hartung, Philipp, Lurz, Philipp, Eitel, Ingo, Marquetand, Christoph, Nef, Holger, Doerr, Oliver, Vigelius-Rauch, Ursula, Lauten, Alexander, Landmesser, Ulf, Treskatsch, Sascha, Abdel-Wahab, Mohamed, Sandri, Marcus, Holzhey, David, Borger, Michael, Ender, Jörg, Ince, Hüseyin, Öner, Alper, Meyer-Saraei, Roza, Hambrecht, Rainer, Wienbergen, Harm, Fach, Andreas, Augenstein, Thomas, Frey, Norbert, König, Inke R., Vonthein, Reinhard, Funkat, Anne-Kathrin, Berggreen, Astrid E., Heringlake, Matthias, Desch, Steffen, de Waha-Thiele, Suzanne, and Thiele, Holger

Published
2021
Full Text
View/download PDF

27. Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients with Oligometastatic Breast Cancer: Study protocol for a randomized controlled multi-national and multi-center clinical trial (OLIGOMA)

Author

Krug, David, Vonthein, Reinhard, Illen, Alicia, Olbrich, Denise, Barkhausen, Jörg, Richter, Julia, Klapper, Wolfram, Schmalz, Claudia, Rody, Achim, Maass, Nicolai, Bauerschlag, Dirk, Heßler, Nicole, König, Inke R., Dellas, Kathrin, and Dunst, Jürgen

Published
2021
Full Text
View/download PDF

31. Identifying genetic modifiers of age-associated penetrance in X-linked dystonia-parkinsonism

Author

Laabs, Björn-Hergen, Klein, Christine, Pozojevic, Jelena, Domingo, Aloysius, Brüggemann, Norbert, Grütz, Karen, Rosales, Raymond L., Jamora, Roland Dominic, Saranza, Gerard, Diesta, Cid Czarina E., Wittig, Michael, Schaake, Susen, Dulovic-Mahlow, Marija, Quismundo, Jana, Otto, Pia, Acuna, Patrick, Go, Criscely, Sharma, Nutan, Multhaupt-Buell, Trisha, Müller, Ulrich, Hanssen, Henrike, Kilpert, Fabian, Franke, Andre, Rolfs, Arndt, Bauer, Peter, Dobričić, Valerija, Lohmann, Katja, Ozelius, Laurie J., Kaiser, Frank J., König, Inke R., and Westenberger, Ana

Published
2021
Full Text
View/download PDF

34. Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA)

Author

Blanck, Oliver, Buergy, Daniel, Vens, Maren, Eidinger, Lina, Zaman, Adrian, Krug, David, Rudic, Boris, Boda-Heggemann, Judit, Giordano, Frank A., Boldt, Leif-Hendrik, Mehrhof, Felix, Budach, Volker, Schweikard, Achim, Olbrich, Denise, König, Inke R., Siebert, Frank-Andre, Vonthein, Reinhard, Dunst, Jürgen, and Bonnemeier, Hendrik

Published
2020
Full Text
View/download PDF

38. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

Motreff, Pascal, Belle, Loïc, Dupouy, Patrick, Barnay, Pierre, Meneveau, Nicolas, Gilard, Martine, Rioufol, Gilles, Range, Grégoire, Brunel, Philippe, Delarche, Nicolas, Filippi, Emmanuelle, Le Bivic, Louis, Harbaoui, Brahim, Benamer, Hakim, Cayla, Guillaume, Varenne, Olivier, Manzo-Silberman, Stephane Peggy, Silvain, Johanne, Spaulding, Christian, Caussin, Christophe, Gerbaud, Edouard, Valy, Yann, Koning, René, Lhermusier, Thibault, Champin, Stanislas, Salengro, Emmanuel, Fluttaz, Arnaud, Zabalawi, Amer, Cottin, Yves, Teiger, Emmanuel, Saint-Etienne, Christophe, Ducrocq, Grégory, Marliere, Stéphanie, Boiffard, Emmanuel, Aubry, Pierre, Georges, Jean Louis, Bresson, Didier, De Poli, Fabien, Karrillon, Gaëtan, Roule, Vincent, Bali, Laurent, Valla, Mathieu, Gerbay, Antoine, Houpe, David, Dubreuil, Olivier, Monnier, Arsène, Mayaud, Norbert, Manchuelle, Aurélie, Commeau, Philippe, Bedossa, Marc, Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M., Willenborg, Christina, Kanoni, Stavroula, Saleheen, Danish, Kyriakou, Theodosios, Nelson, Christopher P., Hopewell, Jemma C., Webb, Thomas R., Zeng, Lingyao, Dehghan, Abbas, Alver, Maris, Armasu, Sebastian M., Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I., Chen, Shufeng, Ford, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Hwang, Shih-Jen, Kim, Yun Kyoung, Kleber, Marcus E., Lau, King Wai, Lu, Xiangfeng, Lu, Yingchang, Lyytikäinen, Leo P., Mihailov, Evelin, Morrison, Alanna, Pervjakova, Natalia, Qu, Liming, Rose, Lynda M., Salfati, Elias, Saxena, Richa, Scholz, Markus, Smith, Albert V., Tikkanen, Emmi, Uitterlinden, Andre, Yang, Xueli, Zhang, Weihua, Zhao, Wei, de Andrade, Mariza, de Vries, Paul S., van Zuydam, Natalie R., Anand, Sonia S., Bertram, Lars, Beutner, Frank, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H., Gottesman, Omri, Haber, Marc, Han, Bok-Ghee, Huang, Jianfeng, Jalilzadeh, Shapour, Kessler, Thorsten, König, Inke R., Lannfelt, Lars, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Lokki, Maisa, Magnusson, Patrik K., Mallick, Nadeem H., Mehra, Narinder, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P., Nieminen, Markku S., Pedersen, Nancy L., Peters, Annette, Rallidis, Loukianos S., Rasheed, Asif, Samuel, Maria, Shah, Svati H., Sinisalo, Juha, Stirrups, Kathleen E., Trompet, Stella, Wang, Laiyuan, Zaman, Khan S., Ardissino, Diego, Boerwinkle, Eric, Borecki, Ingrid B., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Collins, Rory, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Elosua, Roberto, Epstein, Stephen E., Esko, Tõnu, Feitosa, Mary F., Franco, Oscar H., Franzosi, Maria Grazia, Granger, Christopher B., Gu, Dongfeng, Gudnason, Vilmundur, Hall, Alistair S., Hamsten, Anders, Harris, Tamara B., Hazen, Stanley L., Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J., Kim, Bong-Jo, Kooner, Jaspal S., Kullo, Iftikhar J., Lehtimäki, Terho, Loos, Ruth J., Melander, Olle, Metspalu, Andres, März, Winfried, Palmer, Colin N., Perola, Markus, Quertermous, Thomas, Rader, Daniel J., Ridker, Paul M., Ripatti, Samuli, Roberts, Robert, Salomaa, Veikko, Sanghera, Dharambir K., Schwartz, Stephen M., Seedorf, Udo, Stewart, Alexandre F., Stott, David J., Thiery, Joachim, Zalloua, Pierre A., O'Donnell, Christopher J., Reilly, Muredach P., Assimes, Themistocles L., Thompson, John R., Erdmann, Jeanette, Clarke, Robert, Watkins, Hugh, Kathiresan, Sekar, McPherson, Ruth, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J., Farrall, Martin, Adlam, David, Olson, Timothy M., Combaret, Nicolas, Kovacic, Jason C., Iismaa, Siiri E., Al-Hussaini, Abtehale, O'Byrne, Megan M., Bouajila, Sara, Georges, Adrien, Mishra, Ketan, Braund, Peter S., d’Escamard, Valentina, Huang, Siying, Margaritis, Marios, Kadian-Dodov, Daniella, Welch, Catherine A., Mazurkiewicz, Stephani, Jeunemaitre, Xavier, Wong, Claire Mei Yi, Giannoulatou, Eleni, Sweeting, Michael, Muller, David, Wood, Alice, McGrath-Cadell, Lucy, Fatkin, Diane, Dunwoodie, Sally L., Harvey, Richard, Holloway, Cameron, Empana, Jean-Philippe, Jouven, Xavier, Olin, Jeffrey W., Gulati, Rajiv, Tweet, Marysia S., Hayes, Sharonne N., Graham, Robert M., and Bouatia-Naji, Nabila

Published
2019
Full Text
View/download PDF

39. Study protocol to investigate the efficacy of confocal laser endomicroscopy-based selective single-elimination diet over standard fivefold elimination diet in patients with endomicroscopically proven food intolerance: app-assisted, monocentric, double-blind, randomised and controlled trial in Germany

Author

Heßler, Nicole, primary, Kordowski, Anna, additional, Sasse, Jill, additional, Ahlemann, Greta, additional, Schulz, Franziska, additional, Schröder, Torsten, additional, Exner, Anna, additional, Jablonski, Lennart, additional, Jappe, Uta, additional, Bischoff, Stephan C, additional, Grzegorzek, Marcin, additional, König, Inke R, additional, and Sina, Christian, additional

Published
2023
Full Text
View/download PDF

40. Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

Author

Goletz, Stephanie, primary, Pigors, Manuela, additional, Lari, Tina Rastegar, additional, Hammers, Christoph M., additional, Wang, Yao, additional, Emtenani, Shirin, additional, Aumailley, Monique, additional, Holtsche, Maike M., additional, Stang, Felix H., additional, Weyers, Imke, additional, König, Inke R., additional, Has, Cristina, additional, Radzimski, Christiane, additional, Komorowski, Lars, additional, Zillikens, Detlef, additional, and Schmidt, Enno, additional

Published
2023
Full Text
View/download PDF

41. Serum reactivity in dermatitis herpetiformis: an international multicenter study

Author

Boch, Katharina, primary, Heck, Florian, additional, Hammers, Christoph M, additional, Antiga, Emiliano, additional, Caproni, Marzia, additional, Juhl, David, additional, Goletz, Stephanie, additional, Horváth, Orsolya N, additional, Huilaja, Laura, additional, Khil’chenko, Stanislav, additional, Sina, Christian, additional, Tasanen, Kaisa, additional, Vassileva, Snejina, additional, Schlumberger, Wolfgang, additional, Zillikens, Detlef, additional, Shahid, Martin, additional, Drenovska, Kossara, additional, Zone, John J, additional, Koszorú, Kamilla, additional, Fechner, Kai, additional, Dähnrich, Cornelia, additional, König, Inke R, additional, and Schmidt, Enno, additional

Published
2023
Full Text
View/download PDF

43. General versus Local Anesthesia with Conscious Sedation in Transcatheter Aortic Valve Implantation: The Randomized SOLVE-TAVI Trial

Author

Thiele, Holger, Kurz, Thomas, Feistritzer, Hans-Josef, Stachel, Georg, Hartung, Philipp, Lurz, Philipp, Eitel, Ingo, Marquetand, Christoph, Nef, Holger, Doerr, Oliver, Vigelius-Rauch, Ursula, Lauten, Alexander, Landmesser, Ulf, Treskatsch, Sascha, Abdel-Wahab, Mohamed, Sandri, Marcus, Holzhey, David, Borger, Michael, Ender, Jörg, Ince, Hüseyin, Öner, Alper, Meyer-Saraei, Roza, Hambrecht, Rainer, Fach, Andreas, Augenstein, Thomas, Frey, Norbert, König, Inke R., Vonthein, Reinhard, Rückert, Yvonne, Funkat, Anne-Kathrin, Desch, Steffen, Berggreen, Astrid E., Heringlake, Matthias, and de Waha-Thiele, Suzanne

Published
2020
Full Text
View/download PDF

44. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

Author

Liu, Jimmy Z, Hov, Johannes Roksund, Folseraas, Trine, Ellinghaus, Eva, Rushbrook, Simon M, Doncheva, Nadezhda T, Andreassen, Ole A, Weersma, Rinse K, Weismüller, Tobias J, Eksteen, Bertus, Invernizzi, Pietro, Hirschfield, Gideon M, Gotthardt, Daniel Nils, Pares, Albert, Ellinghaus, David, Shah, Tejas, Juran, Brian D, Milkiewicz, Piotr, Rust, Christian, Schramm, Christoph, Müller, Tobias, Srivastava, Brijesh, Dalekos, Georgios, Nöthen, Markus M, Herms, Stefan, Winkelmann, Juliane, Mitrovic, Mitja, Braun, Felix, Ponsioen, Cyriel Y, Croucher, Peter JP, Sterneck, Martina, Teufel, Andreas, Mason, Andrew L, Saarela, Janna, Leppa, Virpi, Dorfman, Ruslan, Alvaro, Domenico, Floreani, Annarosa, Onengut-Gumuscu, Suna, Rich, Stephen S, Thompson, Wesley K, Schork, Andrew J, Næss, Sigrid, Thomsen, Ingo, Mayr, Gabriele, König, Inke R, Hveem, Kristian, Cleynen, Isabelle, Gutierrez-Achury, Javier, Ricaño-Ponce, Isis, van Heel, David, Björnsson, Einar, Sandford, Richard N, Durie, Peter R, Melum, Espen, Vatn, Morten H, Silverberg, Mark S, Duerr, Richard H, Padyukov, Leonid, Brand, Stephan, Sans, Miquel, Annese, Vito, Achkar, Jean-Paul, Boberg, Kirsten Muri, Marschall, Hanns-Ulrich, Chazouillères, Olivier, Bowlus, Christopher L, Wijmenga, Cisca, Schrumpf, Erik, Vermeire, Severine, Albrecht, Mario, UK-PSCSC Consortium, Rioux, John D, Alexander, Graeme, Bergquist, Annika, Cho, Judy, Schreiber, Stefan, Manns, Michael P, Färkkilä, Martti, Dale, Anders M, Chapman, Roger W, Lazaridis, Konstantinos N, International PSC Study Group, Franke, Andre, Anderson, Carl A, Karlsen, Tom H, and International IBD Genetics Consortium

Subjects
UK-PSCSC Consortium, International PSC Study Group, International IBD Genetics Consortium, Humans, Cholangitis, Sclerosing, Oligonucleotide Array Sequence Analysis, Risk Factors, Case-Control Studies, Gene Frequency, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci, Genetic Pleiotropy, Genotyping Techniques, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.

Published
2013

45. Can we predict cognitive decline after initial diagnosis of multiple sclerosis? Results from the German National early MS cohort (KKNMS)

Author

Johnen, Andreas, Bürkner, Paul-Christian, Landmeyer, Nils C., Ambrosius, Björn, Calabrese, Pasquale, Motte, Jeremias, Hessler, Nicole, Antony, Gisela, König, Inke R., Klotz, Luisa, Hoshi, Muna-Miriam, Aly, Lilian, Groppa, Sergiu, Luessi, Felix, Paul, Friedemann, Tackenberg, Björn, Bergh, Florian Then, Kümpfel, Tania, Tumani, Hayrettin, Stangel, Martin, Weber, Frank, Bayas, Antonios, Wildemann, Brigitte, Heesen, Christoph, Zettl, Uwe K., Zipp, Frauke, Hemmer, Bernhard, Meuth, Sven G., Gold, Ralf, Wiendl, Heinz, Salmen, Anke, and German Competence Network Multiple Sclerosis (KKNMS)

Published
2019
Full Text
View/download PDF

47. Identifying rare variants from exome scans: the GAW17 experience

Author

Ghosh, Saurabh, Bickeböller, Heike, Bailey, Julia, Bailey-Wilson, Joan E, Cantor, Rita, Culverhouse, Robert, Daw, Warwick, DeStefano, Anita L, Engelman, Corinne D, Hinrichs, Anthony, Houwing-Duistermaat, Jeanine, König, Inke R, Kent, Jack, Laird, Nan, Pankratz, Nathan, Paterson, Andrew, Pugh, Elizabeth, Suarez, Brian, Sun, Yan, Thomas, Alun, Tintle, Nathan, Zhu, Xiaofeng, Ziegler, Andreas, MacCluer, Jean W, and Almasy, Laura

Abstract

Abstract Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing statistical genetic methods and for developing novel methods to analyze rare variants that modulate complex traits. In this article, we present an overview of the 1000 Genomes Project exome data and simulated phenotype data that were distributed to GAW17 participants for analyses, the different issues addressed by the participants, and the process of preparation of manuscripts resulting from the discussions during the workshop.

Published
2011

48. RANTES/CCL5 and Risk for Coronary Events: Results from the MONICA/KORA Augsburg Case-Cohort, Athero-Express and CARDIoGRAM Studies

Author

Herder, Christian, Peeters, Wouter, Illig, Thomas, Baumert, Jens, de Kleijn, Dominique PV, Moll, Frans L, Poschen, Ulrike, Klopp, Norman, Müller-Nurasyid, Martina, Roden, Michael, Preuss, Michael, Karakas, Mahir, Meisinger, Christa, Thorand, Barbara, Pasterkamp, Gerard, Koenig, Wolfgang, Assimes, Themistocles L, Deloukas, Panos, Erdmann, Jeanette, Holm, Hilma, Kathiresan, Sekar, König, Inke R, McPherson, Ruth, Reilly, Muredach P, Roberts, Robert, Samani, Nilesh J, Schunkert, Heribert, and Stewart, Alexandre FR

Subjects
Cardiovascular, Clinical Research, Genetics, Heart Disease - Coronary Heart Disease, Aging, Heart Disease, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Animals, Calcinosis, Case-Control Studies, Chemokine CCL5, Cohort Studies, Coronary Disease, Female, Follow-Up Studies, Germany, Humans, Macrophages, Male, Mice, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk, CARDIoGRAM Consortium, General Science & Technology
Abstract

BackgroundThe chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events.Methods and findingsWe conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years).ConclusionsHigh RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies.

Published
2011

49. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author

Lango Allen, Hana, Estrada, Karol, Lettre, Guillaume, Berndt, Sonja I, Weedon, Michael N, Rivadeneira, Fernando, Willer, Cristen J, Jackson, Anne U, Vedantam, Sailaja, Raychaudhuri, Soumya, Ferreira, Teresa, Wood, Andrew R, Weyant, Robert J, Segrè, Ayellet V, Speliotes, Elizabeth K, Wheeler, Eleanor, Soranzo, Nicole, Park, Ju-Hyun, Yang, Jian, Gudbjartsson, Daniel, Heard-Costa, Nancy L, Randall, Joshua C, Qi, Lu, Vernon Smith, Albert, Mägi, Reedik, Pastinen, Tomi, Liang, Liming, Heid, Iris M, Luan, Jian’an, Thorleifsson, Gudmar, Winkler, Thomas W, Goddard, Michael E, Sin Lo, Ken, Palmer, Cameron, Workalemahu, Tsegaselassie, Aulchenko, Yurii S, Johansson, Åsa, Carola Zillikens, M, Feitosa, Mary F, Esko, Tõnu, Johnson, Toby, Ketkar, Shamika, Kraft, Peter, Mangino, Massimo, Prokopenko, Inga, Absher, Devin, Albrecht, Eva, Ernst, Florian, Glazer, Nicole L, Hayward, Caroline, Hottenga, Jouke-Jan, Jacobs, Kevin B, Knowles, Joshua W, Kutalik, Zoltán, Monda, Keri L, Polasek, Ozren, Preuss, Michael, Rayner, Nigel W, Robertson, Neil R, Steinthorsdottir, Valgerdur, Tyrer, Jonathan P, Voight, Benjamin F, Wiklund, Fredrik, Xu, Jianfeng, Hua Zhao, Jing, Nyholt, Dale R, Pellikka, Niina, Perola, Markus, Perry, John RB, Surakka, Ida, Tammesoo, Mari-Liis, Altmaier, Elizabeth L, Amin, Najaf, Aspelund, Thor, Bhangale, Tushar, Boucher, Gabrielle, Chasman, Daniel I, Chen, Constance, Coin, Lachlan, Cooper, Matthew N, Dixon, Anna L, Gibson, Quince, Grundberg, Elin, Hao, Ke, Juhani Junttila, M, Kaplan, Lee M, Kettunen, Johannes, König, Inke R, Kwan, Tony, Lawrence, Robert W, Levinson, Douglas F, Lorentzon, Mattias, McKnight, Barbara, Morris, Andrew P, Müller, Martina, Suh Ngwa, Julius, Purcell, Shaun, Rafelt, Suzanne, Salem, Rany M, and Salvi, Erika

Subjects
Biological Sciences, Genetics, Health Sciences, Mathematical Sciences, Statistics, Human Genome, Clinical Research, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Body Height, Chromosomes, Human, Pair 3, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Metabolic Networks and Pathways, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results