Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Solveig K. Sieberts, Fan Zhu, Javier García-García, Eli Stahl, Abhishek Pratap, Gaurav Pandey, Dimitrios Pappas, Daniel Aguilar, Bernat Anton, Jaume Bonet, Ridvan Eksi, Oriol Fornés, Emre Guney, Hongdong Li, Manuel Alejandro Marín, Bharat Panwar, Joan Planas-Iglesias, Daniel Poglayen, Jing Cui, Andre O. Falcao, Christine Suver, Bruce Hoff, Venkat S. K. Balagurusamy, Donna Dillenberger, Elias Chaibub Neto, Thea Norman, Tero Aittokallio, Muhammad Ammad-ud-din, Chloe-Agathe Azencott, Víctor Bellón, Valentina Boeva, Kerstin Bunte, Himanshu Chheda, Lu Cheng, Jukka Corander, Michel Dumontier, Anna Goldenberg, Peddinti Gopalacharyulu, Mohsen Hajiloo, Daniel Hidru, Alok Jaiswal, Samuel Kaski, Beyrem Khalfaoui, Suleiman Ali Khan, Eric R. Kramer, Pekka Marttinen, Aziz M. Mezlini, Bhuvan Molparia, Matti Pirinen, Janna Saarela, Matthias Samwald, Véronique Stoven, Hao Tang, Jing Tang, Ali Torkamani, Jean-Phillipe Vert, Bo Wang, Tao Wang, Krister Wennerberg, Nathan E. Wineinger, Guanghua Xiao, Yang Xie, Rae Yeung, Xiaowei Zhan, Cheng Zhao, Jeff Greenberg, Joel Kremer, Kaleb Michaud, Anne Barton, Marieke Coenen, Xavier Mariette, Corinne Miceli, Nancy Shadick, Michael Weinblatt, Niek de Vries, Paul P. Tak, Danielle Gerlag, Tom W. J. Huizinga, Fina Kurreeman, Cornelia F. Allaart, S. Louis Bridges, Lindsey Criswell, Larry Moreland, Lars Klareskog, Saedis Saevarsdottir, Leonid Padyukov, Peter K. Gregersen, Stephen Friend, Robert Plenge, Gustavo Stolovitzky, Baldo Oliva, Yuanfang Guan and Lara M. Mangravite
Additional contact information
Solveig K. Sieberts: Sage Bionetworks
Fan Zhu: University of Michigan
Javier García-García: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Eli Stahl: Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai
Abhishek Pratap: Sage Bionetworks
Gaurav Pandey: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai
Dimitrios Pappas: Columbia University
Daniel Aguilar: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Bernat Anton: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Jaume Bonet: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Ridvan Eksi: University of Michigan
Oriol Fornés: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Emre Guney: Center for Complex Network Research, Northeastern University
Hongdong Li: University of Michigan
Manuel Alejandro Marín: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Bharat Panwar: University of Michigan
Joan Planas-Iglesias: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Daniel Poglayen: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Jing Cui: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Andre O. Falcao: Faculty of Sciences, University of Lisbon
Christine Suver: Sage Bionetworks
Bruce Hoff: Sage Bionetworks
Venkat S. K. Balagurusamy: IBM T.J. Watson Research Center, Yorktown Heights
Donna Dillenberger: IBM T.J. Watson Research Center, Yorktown Heights
Elias Chaibub Neto: Sage Bionetworks
Thea Norman: Sage Bionetworks
Tero Aittokallio: IBM T.J. Watson Research Center, Yorktown Heights
Muhammad Ammad-ud-din: Aalto University
Chloe-Agathe Azencott: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
Víctor Bellón: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
Valentina Boeva: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
Kerstin Bunte: Aalto University
Himanshu Chheda: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Lu Cheng: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Jukka Corander: Helsinki Institute for Information Technology (HIIT)
Michel Dumontier: Stanford Center for Biomedical Informatics, Stanford University
Anna Goldenberg: University of Toronto
Peddinti Gopalacharyulu: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Mohsen Hajiloo: Genetics and Genome Biology, SickKids Research Institute
Daniel Hidru: University of Toronto
Alok Jaiswal: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Samuel Kaski: Aalto University
Beyrem Khalfaoui: Genetics and Genome Biology, SickKids Research Institute
Suleiman Ali Khan: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Eric R. Kramer: The Scripps Translational Science Institute, The Scripps Research Institute
Pekka Marttinen: Aalto University
Aziz M. Mezlini: University of Toronto
Bhuvan Molparia: The Scripps Translational Science Institute, The Scripps Research Institute
Matti Pirinen: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Janna Saarela: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Matthias Samwald: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna
Véronique Stoven: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
Hao Tang: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Jing Tang: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Ali Torkamani: The Scripps Translational Science Institute, The Scripps Research Institute
Jean-Phillipe Vert: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
Bo Wang: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Tao Wang: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Krister Wennerberg: Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Nathan E. Wineinger: The Scripps Translational Science Institute, The Scripps Research Institute
Guanghua Xiao: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Yang Xie: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Rae Yeung: Institute of Medical Sciences, University of Toronto
Xiaowei Zhan: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
Cheng Zhao: University of Toronto
Jeff Greenberg: Sage Bionetworks
Joel Kremer: Albany Medical College
Kaleb Michaud: University of Nebraska Medical Center
Anne Barton: Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester
Marieke Coenen: Radboud University Nijmegen Medical Centre
Xavier Mariette: Université Paris-Sud
Corinne Miceli: Université Paris-Sud
Nancy Shadick: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Michael Weinblatt: Immunology, and Allergy, Brigham and Women’s Hospital, Harvard Medical School
Niek de Vries: Academic Medical Center/University of Amsterdam
Paul P. Tak: Academic Medical Center/University of Amsterdam
Danielle Gerlag: Academic Medical Center/University of Amsterdam
Tom W. J. Huizinga: Leiden University Medical Centre
Fina Kurreeman: Leiden University Medical Centre
Cornelia F. Allaart: Merck Research Labs, Merck and Co., Inc., Boston
S. Louis Bridges: University of Alabama at Birmingham, Birmingham
Lindsey Criswell: Rosalind Russell/Ephraim P Engleman Rheumatology Research Center, University of California San Francisco
Larry Moreland: University of Pittsburgh, Pittsburgh
Lars Klareskog: Rheumatology Unit, Karolinska Hospital and Karolinska Institutet
Saedis Saevarsdottir: Rheumatology Unit, Karolinska Hospital and Karolinska Institutet
Leonid Padyukov: Rheumatology Unit, Karolinska Hospital and Karolinska Institutet
Peter K. Gregersen: Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, North Shore LIJ Health System
Stephen Friend: Sage Bionetworks
Robert Plenge: Merck Research Labs, Merck and Co., Inc., Boston
Gustavo Stolovitzky: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai
Baldo Oliva: Structural Bioinformatics Group (GRIB/IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Yuanfang Guan: University of Michigan
Lara M. Mangravite: Sage Bionetworks

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge ( http://www.synapse.org/RA_Challenge ). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

Date: 2016
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DOI: 10.1038/ncomms12460

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