Publications in Precision Medicine

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RA Responder Challenge
May 2013

Crowdsourcing genetic prediction of clinical utility in the Rheumatoid Arthritis Responder Challenge, Plenge RM, Greenberg JD, Mangravite LM, Derry JM, Stahl EA, Coenen MJ, Barton A, Padyukov L, Klareskog L, Gregersen PK, Mariette X, Moreland LW, Bridges SL Jr, de Vries N, Huizinga TW, Guchelaar HJ; International Rheumatoid Arthritis Consortium (INTERACT), Friend SH, Stolovitzky G. Nat Genet. 2013 Apr 26;45(5):468-9. doi: 10.1038/ng.2623. PMID: 23619782.

We announce a new collaboration between PGRN, Sage Bionetworks, DREAM, the Arthritis Foundation, CORRONA, and others.  The goal is to use crowdsourcing to identify genetic predictors of response to anti-TNF therapy in RA.

anti-TNF GWAS in RA
March 2013

Genome-Wide Association Study and Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis, Cui J, Stahl EA, Saevarsdottir S, Miceli C, Diogo D, Trynka G,  Raj T, Umiċeviċ-Mirkov M, Canhao H, Ikari K, Terao C, Okada Y, Wedrén S, Askling J, Yamanaka H, Momohara S, Taniguchi A, Ohmura K, Matsuda F, Mimori T, Gupta N, Kuchroo M, Morgan AW, Isaacs JD, Wilson AG, Hyrich KL, Herenius M, Doorenspleet ME, Tak PP, Crusius JBA, van der Horst-Bruinsma IE, Wolbink GT, van Riel PLCM, van de Laar M, Guchelaar HJ, Shadick NA, Allaart CF, Huizinga TWJ, Toes REM, Kimberly RP, Bridges Jr SL, Criswell LA, Moreland LW, Fonseca JE, de Vries N, Stranger BE, De Jager PL, Raychaudhuri S, Weinblatt ME, Gregersen PK, Mariette X, Barton A, Padyukov L, Coenen MJH, Karlson EW, Plenge RM. PLoS Genetics. published 28 Mar 2013.

We found evidence that a common, non-coding variant near the CD84 gene influences response to one anti-TNF drug (etanercept).  The same variant is an eQTL for the CD84 gene.

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GWAS of response to anti-TNF therapy
December 2012

Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis, Umicevic Mirkov M, Cui J, Vermeulen SH, Stahl EA, Toonen EJ, Makkinje RR, Lee AT, Huizinga TW, Allaart R, Barton A, Mariette X, Miceli CR, Criswell LA, Tak PP, de Vries N, Saevarsdottir S, Padyukov L, Bridges SL, van Schaardenburg DJ, Jansen TL, Dutmer EA, van de Laar MA, Barrera P, Radstake TR, van Riel PL, Scheffer H, Franke B, Brunner HG, Plenge RM, Gregersen PK, Guchelaar HJ, Coenen MJ. Ann Rheum Dis. 2012 Dec 11. [Epub ahead of print] PMID: 23233654

Led by our colleague Dr. Marieke Coenen in the Netherlands, this is a GWAS of response to anti-TNF therapy in the DREAM cohort.

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Candidate gene study of response to anti-TNF therapy
September 2012

Association of Rheumatoid Arthritis Risk Alleles with Response to Anti-TNF Biologics: Results from the CORRONA Registry and Meta-analysis, Pappas DA, Oh C, Plenge RM, Kremer JM, Greenberg JD. Inflammation. 2012 Sep 25. [Epub ahead of print] PMID: 23007924

Led by Jeff Greenberg and colleagues at CORRONA, we tested RA risk alleles for association with response to anti-TNF therapy. 

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The Brigham Rheumatoid Arthritis Sequential Study (BRASS) registry
January 2011

Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study. Iannaccone CK, Lee YC, Cui J, Frits ML, Glass RJ, Plenge RM, Solomon DH, Weinblatt ME, Shadick NA Rheumatology 2011 Jan;50(1):40-6. PMID: 20847201

This manuscript describes the BRASS cohort, which we use in our genetic studies of response to therapy in RA.

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PTPRC gene and response to anti-TNF therapy
July 2010

PTPRC rheumatoid arthritis risk allele is also associated with response to anti-TNF therapy. Cui J, Saevarsdottir S, Thomson B, Padyukov L, van der Helm-van Mil AH, Nititham J, Hughes LB, de Vries N, Raychaudhuri S, Alfredsson L, Askling J, Wedrén S, Ding B, Guiducci C, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Herenius M, Weinblatt ME, Shadick NA, Worthington J, Batliwalla F, Kern M, Morgan AW, Wilson AG, Isaacs JD, Hyrich K, Seldin MF, Moreland LW, Behrens TW, Allaart CF, Criswell LA, Huizinga TW, Tak PP, Bridges SL Jr, Toes RE, Barton A, Klareskog L, Gregersen PK, Karlson EW, Plenge RM.  Arthritis Rheum. 2010 Jul;62(7):1849-61. PMID: 20309874

We examined RA risk SNPs for evidence of association to response to anti-TNF therapy.  We found suggestive evidence that one SNP in the PTPRC gene (aka CD45) influenced both phenotypes.

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HapMap cell lines
November 2008

Genetic Analysis of Human Traits In-Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines. Choy E, Yelensky R, Bonakdar S, Plenge RM, Saxena R, De Jager PL, Shaw SY, Wolfish CS, Slavik JM, Cotsapas C, Rivas M, Dermitzakis ET, Cahir-McFarland E, Kieff E, Hafler D, Daly MJ, and Altshuler D. PLoS Genet. 2008 Nov;4(11):e1000287. PMID: 19043577

We examined whether drug response is heritable in HapMap cell lines.

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GWAS of anti-TNF therapy
September 2008

Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in Rheumatoid Arthritis. Liu C, Batliwalla F, Li W, Lee A, Roubenoff R, Beckman E, Khalili H, Damle A, Kern M, Plenge RM, Coenen M, Behrens TW, Furie R, Carulli JP, Gregersen PK. Mol Med. 2008 Sep-Oct;14(9-10):575-81. PMID: 18615156

This is a small GWAS of response to anti-TNF therapy in RA. Nonetheless, it set the stage for future GWAS.

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