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

Author

Listed:
  • 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
    Icahn Institute for Genomics and Multiscale Biology, 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
    Icahn School of Medicine at Mount Sinai)

  • Dimitrios Pappas

    (Columbia University
    Corrona LLC,)

  • 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
    Helsinki Institute for Information Technology (HIIT))

  • Chloe-Agathe Azencott

    (MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
    Institut Curie
    Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, INSERM U900)

  • Víctor Bellón

    (MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
    Institut Curie
    Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, INSERM U900)

  • Valentina Boeva

    (MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology
    Institut Curie
    Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, INSERM U900)

  • Kerstin Bunte

    (Aalto University
    Helsinki Institute for Information Technology (HIIT))

  • Himanshu Chheda

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki)

  • Lu Cheng

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki
    Aalto University
    Helsinki Institute for Information Technology (HIIT))

  • Jukka Corander

    (Helsinki Institute for Information Technology (HIIT)
    University of Helsinki)

  • Michel Dumontier

    (Stanford Center for Biomedical Informatics, Stanford University)

  • Anna Goldenberg

    (University of Toronto
    Genetics and Genome Biology, SickKids Research Institute)

  • 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
    Genetics and Genome Biology, SickKids Research Institute)

  • Alok Jaiswal

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki)

  • Samuel Kaski

    (Aalto University
    Helsinki Institute for Information Technology (HIIT)
    University of Helsinki)

  • Beyrem Khalfaoui

    (Genetics and Genome Biology, SickKids Research Institute)

  • Suleiman Ali Khan

    (Institute for Molecular Medicine Finland (FIMM), University of Helsinki
    Aalto University
    Helsinki Institute for Information Technology (HIIT))

  • Eric R. Kramer

    (The Scripps Translational Science Institute, The Scripps Research Institute)

  • Pekka Marttinen

    (Aalto University
    Helsinki Institute for Information Technology (HIIT))

  • Aziz M. Mezlini

    (University of Toronto
    Genetics and Genome Biology, SickKids Research Institute)

  • 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
    Institut Curie
    Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, INSERM U900)

  • 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
    Institut Curie
    Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, INSERM U900)

  • 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
    Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center)

  • Rae Yeung

    (Institute of Medical Sciences, University of Toronto
    Cell Biology, SickKids Research Institute)

  • Xiaowei Zhan

    (Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center
    Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center)

  • Cheng Zhao

    (University of Toronto
    Genetics and Genome Biology, SickKids Research Institute)

  • Jeff Greenberg

    (Sage Bionetworks
    New York University School of Medicine)

  • Joel Kremer

    (Albany Medical College)

  • Kaleb Michaud

    (University of Nebraska Medical Center
    National Data Bank for Rheumatic Diseases)

  • Anne Barton

    (Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester
    NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust)

  • Marieke Coenen

    (Radboud University Nijmegen Medical Centre)

  • Xavier Mariette

    (Université Paris-Sud
    APHP–Hôpital Bicêtre, Center of Immunology of Viral Infections and Autoimmune Diseases (IMVA) INSERM U1184)

  • Corinne Miceli

    (Université Paris-Sud
    APHP–Hôpital Bicêtre, Center of Immunology of Viral Infections and Autoimmune Diseases (IMVA) INSERM U1184)

  • 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
    Cambridge University
    Ghent University
    GlaxoSmithKline)

  • Danielle Gerlag

    (Academic Medical Center/University of Amsterdam
    Clinical Unit, GlaxoSmithKline)

  • 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 Jr.

    (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
    Icahn School of Medicine at Mount Sinai
    Faculty of Sciences, University of Lisbon)

  • 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)

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.

Suggested Citation

  • 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 , 2016. "Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12460
    DOI: 10.1038/ncomms12460
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